Chapter 6 – Cell Signaling

okay so we’ve talked a lot about cells and we’ve talked about chemistry of course and when we talked about cells we talked about some of the organelles so we had the cell and then we had the nucleus and then we had things like the ER and the Golgi and then we talked about secretion of certain things okay so and we kind of stopped there so now it’s time to talk about what these things might be doing okay so we know that cells usually are in groups whether it’s epithelial cells or a lot of times like in your lymph nodes you have different immune cells and these guys have to communicate with each other so everybody knows what’s going on okay so we have to know about this on some level because that’s where drugs have their effect so if you’re if you’re talking about like a neuron the neuron will communicate with another neuron and there are chemicals that are released neurotransmitters and so there have to be a some kind of receptor here so this one can communicate with this one okay and so that happens in your liver it happens all over the place every single every single cell is somehow communicating with the other cells around us we’re going to talk about some of those things okay so when we talk about I guess the reasons and the mechanisms for how these cells communicate remember we’ve mentioned that the inside of the cell is about about minus 70 millivolts okay if that changes if that goes up or if that goes down that cell has some kind of an effect okay so that cells going to have some kind of response that means something to the cell so and we call that a change in the membrane potential okay so this area across here this is a potential okay so so that’s the ability for charges to move so ions might move in here and that might make it minus 60 okay and so that’s how neurons know what to do that’s how they communicate that’s how they function that’s how muscle cells function and that’s how other cells functions including things like the during fertilization there’s there’s a change in the in the potential okay and then there are also chemical signals okay so like the neuron okay so there’s an electrical signal that’s happening down this axon and up here in the cell body but then there are neuro neurotransmitters that are released and that’s going to be a chemical signal okay so that’s release secreted by cells into the extracellular fluid okay so that’s what’s happening there and then of course as I mentioned immune cells they have to communicate with other immune cells and so you have a response okay and so they’re going to change some of their intracellular functions so they do something different like attack like a bacteria or a virus or something and wipe it out all right so recycle signals are responsible for most communication now we’re going to talk about the electrical signaling when we cover narrow the neuro part of things and when we talk about muscles and when we talk about heart even and so there have to be target cells so if this cell releases a signal it has to have a target when this neurotransmitter releases its signal it has to have a target okay so this is its target and it may have it may branch out it may have a whole bunch of target so there has to be a target cell and something to receive that signal so we have to discuss some terms okay so here you can see this cell down here this guy right here and somehow the cell signaling always I mean there’s a communication coming in and there’s a communication leaving so somehow this guy got a signal or something that said okay I need to release a signaling molecule okay so this is what this guy this is right here this is a signaling molecule now if you look at this this signaling molecule can actually bind to the same cell that just released the signaling molecule and this happens it’s called autocrine signaling Auto means self okay so it signals itself now or it may and usually it does both it may signal other cells so this cell over here is receiving the signal and then this cell is receiving the signal now if it’s acting on another cell in the area so or adjacent cell some kind of cell in the area we call that para Crenn paracrine signaling so the only difference between autocrine and paracrine is autocrine is actually being released by the cell and then it affects that cell pair credits release it it’s released by a cell and it’s affecting

other cells in the area okay so they have to be close or what we would say is local cell to cell communication and I’ll just say very quickly a lot of people wonder why a cell would release a molecule and then bind to itself probably because this cell has two different communication types of functions okay so it gets a signal in and then it causes it to release a molecule okay now it’s releasing this molecule so it can tell these cells hey guys something happened to me and I need to tell you about it so you could have some kind of a response okay okay so if this one this one also it’s the same kind of cell so it also has to have a response now rather than having a separate mechanism in here which tells it to respond it just has it uses the same method as everything else and it has this method that then tells it to respond so if that makes any sense you have a signal coming in saying hey something’s going on and it has two things that it can do it can send out a signal and once it receives a signal it can respond okay and that’s all any of these cells need all this one needs is oh I got a signal I can respond the only other job I can do is release a signal okay so two things this one if it were if it were going to have a different mechanism it would have to say oh I received a signal now I’m going to have to have a completely different mechanism so I can respond or I can just use the thing I already have I already have a receptor up here that causes me to respond so I’ll just use that and so it’s a much simpler way to have an autocrine signal and so that does pose a lot of questions for people why autocrine signals happen and it’s because you don’t have to have a third intracellular mechanism you can just use this one up here okay so I hope that makes sense so those are autocrine and paracrine and those are local now what if we have to communicate with something a long ways away okay so what if we have to change our digestion and we want to release a signal say from the pituitary gland or from the thyroid gland or something like that and that happens through and this is the important thing here the blood okay so think about that the blood goes everywhere in the body so all you need to do is you need to have an area we call it an endocrine cell or an endocrine gland like the thyroid gland and the pancreas has some endocrine function it releases insulin and glucagon and so we can have this sitting here in a localized area a lot of times normally and it will release a molecule and that molecule can go all over the body okay so the thyroid gland affects lots of different areas but it’s just located in one little area this is supposed to be a person it’s just located in one little area under in the neck area okay so that’s that’s a guy and that’s his neck okay and that’s the thyroid gland so that can be released and then it can have its effect in lots of places okay alright so the question is if you’re releasing it into the blood it’s going to affect every cell right well the answer is no because you have to have some kind of a receptor now this cell until I drew it doesn’t have a receptor so it’s not going to be affected mm-hmm this cell over here has a receptor and so it’s going to have a response and that’s very important because that’s where the control comes from okay so that’s why you can have the thyroid gland just sitting up here in your neck and you can affect cells anywhere else in the body okay and it’s because that’s where the receptors are okay so the important thing here it’s thing I really want you to understand is that when you’re talking about hormones you’re talking about long-distance signaling and hormones are by definition released into the blood okay so they’re not just released into the extracellular fluid around them they’re released into the blood they have to make their way into the blood so they can go everywhere okay now we have another set of hormones and you’ll hear this sometimes neurohormones things like epinephrine they’ll release they release into the blood just like a hormone so there’s still a hormone they’re still releasing it into the bloodstream however in this case they’re releasing a pseudo from an endocrine cell or an endocrine gland which are made up of endocrinology and then because it’s released from a neuron so hopefully that makes sense and

it’s the same deal if there’s a receptor it has an effect if there’s earth if there is a receptor like in this case it has an effect if there is no receptor it doesn’t matter this one just doesn’t do anything it doesn’t change anything it’s been doing okay so now we’re told we’ve we’ve talked a little bit about neurons and we’ve said that the neuron can release a molecule into the blood and that makes it a neuro hormone well if it’s released from a neuron into the extracellular fluid and not into the blood and it just has its effect on the next neuron or cell okay so usually and I say that because it’s your numbers usually a neuron communicates with another neuron but it doesn’t have to a neuron can sometimes release a neurotransmitter okay so that makes sense neuro and it’s transmitting so a neurotransmitter directly onto any kind of cell okay now we have so many neurons that it’s usually neuron to neuron but but this can take place okay and so they have a very rapid effect it happens right away and then the like I said they have an electrical signal and we call this an action potential we’ll talk more about that when we talk about the talk about the neuro section so it has an action potential that runs down the neuron and that’s electrical and then we’re down the axon and then the neurotransmitters release and it has its effect okay so it’s very very fast it’s very immediate that’s why we’re able to think okay so we’ve covered covered autocrine paracrine and then hormones neural hormones and neurotransmitters okay so we have other types of cell to cell communication and this one is very very important for function I mean of course everything is important you can’t survive without neurons but these are called cytokines cytokines were actually first found in the immune system okay so that’s that’s where we that’s where we know them okay so that’s how we discovered them we I wasn’t there but that’s how they were discovered is in the immune system and they were trying to figure out how all of these cells and you don’t have to know all of these all of these pathways but it shows you how complicated it could be they were wondering how all these immune cells knew so when one cell was affected you know when it when a bacteria or a virus invaded it would have a response and it would tell all of the other cells to respond okay so and then you had this huge immune response and that’s why we have you know swelling of our lymph nodes because that’s where a lot of these these cells kind of rest and that’s where they stay most of the time and so they would start to divide they would have this huge effect so then we knew there was some kind of signaling going on and so it was a process of trying to figure out what these signals were okay and we finally found them they finally found them and they just and they called them cytokines okay and then they figured out that and this is this is important that all nucleated cells actually produce these cytokines and now they may affect the cells in the area which is what this kind of shows or they may have long-distance signaling so they may affect cells in lots of different places of the body so they can’t we can’t really call them auto print paracrine which is close or local and we can’t really call them hormones and so they have their own they have their own little category and they have their own names they’re usually called like il which stands for interleukin which means between white blood cells and some are just called you know cytokines okay and there are a lot of diseases associated with like for instance this one I don’t know if you can read this but it says wait not that one if you have there’s there’s one called il-2 interleukin 2 and I don’t see any on here which is very important for an immune and immune response okay I thought that we had one on there but apparently we don’t so so you can see here that there’s a microbial infection or yeast infection or bacteria or a virus here so bacteria yeast virus and and you can see that this is affected and it will release this interleukin or this cytokine okay and then it will have an inflammatory response okay all right so if we have if we look at just in general how these things have their effects we have to have a cell that releases whatever it’s releasing whether it’s a cytokine or a neurotransmitter or

something it has to have a way to affect the next cell okay so now sometimes if it’s a hydrophilic which is another which they’re calling it Lippo phobic here but that’s also hydrophilic okay signal then it has to bind to a receptor has to bind to a receptor now and so when it binds to this receptor then it’ll have its effect inside the cell now this is going to be on quizzes tests something and it always confuses people okay so hopefully we understand this difference between hydrophobic and hydrophilic okay hydrophilic remember hydrophilic means that it likes water it’s attracted to water because of the chemical because of the electrical properties hydrophobic means that it doesn’t really care about water okay so this is hydrophobic in this case they’re calling it lipophilic which means that it likes lipids okay so it’s so it is soluble and lipids it´ll and what that means for us is that this hydrophobic slash also lipophilic signal will go right through the membrane which is very important because things like estrogens a lot of the steroid molecules they just are released into the blood and they’ll just go all the way through cells it doesn’t really matter so if that’s the case then you can have a receptor inside the cell you can even have a receptor inside the nucleus and so this molecule right here because a lot of steroids actually turn on or off DNA so they just have their signal or their receptor right in here and you don’t have to mess with anything else okay so only lipophilic molecules can do that only if they can move through this cell membrane now if it’s hydrophilic now lip a lipophilic hydrophobic are also listed here okay so I circled it up here and I said look they can go all the way through this is the part that confuses people though is that here you can also see that sometimes they have a receptor that’s out here on the membrane it’s as though they can’t get through now this is probably because it’s it’s they don’t go through as well okay so you know that they can get the signal if they just have if they just bind to a receptor on the outside of the membrane so I hope that makes sense so that means that lipophilic which I labeled here and lipophilic which I label here they can either go through the membrane or they can bind to a receptor on the outside they can do any of them now if we look at the other ones if we look at the hydrophilic which in this case they’re talking about Lippo because they want to make it clear that it’s the lipid that it’s either likes the lipid or it doesn’t like the lipid lipid so hydrophilic which is the same as lipeh phobic I didn’t invent all these terms I just try to help you keep them straight and I try to keep them straight myself if a lip of phobic that means that it can’t that means that if this thing were to try to go through here it wouldn’t it would just bounce right off okay it’s not able to penetrate the membrane it can only only bind to a receptor on the outside of the cell so if it’s lipid soluble lipeh phobic it can do any of these it can go in into the cytosol I can go into the nucleus air or it can bind to a receptor if it’s hydrophilic or what we would say lipeh phobic it has to bind to a receptor on the outside of the cell and then this will communicate with the inside of the cell so that’s what we’re gonna talk about next okay so if you look at the different kinds of receptors there are because remember our goal is to have some kind of an effect inside the cell so we want to have an effect inside the cell so now we have these channels where if you look at this little molecule here this is extracellular so it could be could have been released from anywhere Autocar and Parrikar and hormonal whatever neurotransmitter so here’s the molecule and it can bind to a little receptor and when it binds the receptor it can have an effect okay so here’s another one in this case this is an enzyme so so you have a molecule from outside the cell activating an enzyme inside the cell

which is going to have and effect okay this is another one and this is this is what I’m going to talk about in a bit it’s called a g-protein coupled receptor and this can have their your binding happens here and it will activate this which has an effect inside the cell this I believe is a tyrosine kinase and which is a different kind of molecule but it’s the same thing so it has oh this is an Integra and so it’s going it can have an effect on the inside of the cell or the or the cell structure okay now once we get the signal into the cell so if we look at this so it converts a chemical signals so from outside okay into a cellular spot a response which is inside okay so here’s our signaling molecule if we look up here here’s our signaling molecule it binds to a receptor and then it can have a whole lot of responses inside the cell okay lots of things can happen it can it can actually cause a cell response directly which is what we see here or it can actually open up another channel see this guy there’s no receptor up here for it or there might be it might need to do both so or this may not have any receptor at all and by activating this one over here you might you might activate this and this will then open that channel so somehow we’re having a signal and that’s the big deal we’re having a signal from the outside that’s having an effect on the inside which is causing the cell to response so I want to say a little more about this g-protein coupled receptor because there are questions on it on the exam and the quiz is about this it’s seven transmembrane so what that means it’s it’s a protein this is a protein itself and the way that it’s structured it crosses the membrane one two three four five six seven times and then there’s a little tail that’s inside so the receptor will bind up here and it’ll cause some kind of a shape change what we call a conformational change that will activate a g-protein so g-protein is just a gtp instead of an ATP okay so we’re not we’re not too concerned about that but that’s or it hydrolyzes GTV so we’re not too concerned about this but that’s but that’s what it is and that’s why it’s called this because we call this a g-protein it has a few different subunits but then this will go on to cause something else to happen okay so there’s a cytoplasmic tail of the GPC our g-protein coupled receptor that will then affect what we call a transducer or a signal communicator molecule so this will communicate the signal to the rest of the cell okay so they can do lots of things open ion channels in the membrane alter enzymes act enzyme activity on the cytoplasmic side of the membrane but they’re doing something to the cell now the reason that I that I talk so much or I mention g-protein coupled receptors gpcrs is because about half of drugs work on these okay so we’re gonna see things like agonists and antagonists and so you could take a drug that may activate this or antagonize it or you could take a drug that blocks blocks it okay so if it activates I may have said that wrong I don’t remember but if it if it activates it it’s an agonist I think I may have said that backwards and if it just kind of gets in the way so it just kind of blocks it that’s an antagonist okay and like I said about half the drugs will have an effect half the drugs that we take have this effect because these are everywhere and they do a lot of different things but in general we say that they activate the inside of the cell they do something inside the cell okay so here’s some examples and this is again why they’re so important again we’re still talking about g-protein coupled receptors and so you can see here that there’s a signal molecule one signal molecule now if you’re looking ahead ahead of me you can see that that one signal molecule has had a large effect okay so it’s activated its g-protein that’s why it’s called a g-protein coupled receptor because this is the g-protein which activates another enzyme this is this enzymes called adenyl cyclase which turns ATP into something called cyclic a MP which activates a kinase kinase is put foss foss phosphate groups on things so we say that’s phosphorylate at a different protein

which then goes on to activate something else which then goes on to activate something else okay so you don’t have to know all of these mechanisms but you do have to know that that’s what AG PCR does okay so it does it can cause a huge effect on the inside of the cell even though it’s just one molecule this one little molecule binds and has and activates all of this okay so that’s one way that they work there are only a few different ways that they work so it’s not impossible to learn but I think usually you learn that in a in a regular biology class or a cell biology class or something like that I just want to either remind you about them or make you aware that these things exist and so and to get that gpcr g-protein coupled receptor name into your head the seven transmembrane tied to a g-protein okay so here’s a different mechanism that they use so in this case it’s activating something called phospholipase C in protein kinase C ip3 which is called an assault rifle fate lots of big names you don’t have to know all these I’m not going to ask you about these but you can see in this case this is actually the goal of this when this guy binds is to release calcium okay calcium is a signaling molecule okay okay so calcium is a signaling molecule and it’s going to have lots of effects okay so this just says cellular response which works for us and and so together there’s also phosphorylation that takes place so lots of lots of different things and I don’t I don’t mean to confuse you by it but I just want to want you to see that there’s some range to what gpcrs do but ultimately they cause big changes inside okay okay I don’t know if that’s a that’s a formal term but that’s what they do they tend to change the inside of the cell okay sometimes they can be sometimes they can be very quick like in this case they have their effect fairly quickly so here’s a this is what I said this is a channel molecule and so even though this binds it may not activate okay it may be waiting for a signal from the inside so you have to have something else the binds to the GPCR which causes a cascade of responses but one of those things is to go up here and open that okay and then it’ll let yawns in or out okay and so that changes the membrane potential now this would happen very quickly okay so it binds and then it immediately opens that signal and a lot of things like I said these are everywhere we if you’ve heard of dopamine or serotonin a lot of dopamine and serotonin neurotransmitters that’s what so what those are will have their effect this way okay they may not even bind that there may not even be any binding to the receptor it may but they’re to the channel it may bind to the G protein-coupled receptor cause a whole bunch of stuff to be released and then keep that channel open for quite a while okay so there are lots of different ways lots of variability and diversity in the way these guys work okay all right now some other signaling molecules and I try to only talk about things that are that are somehow relevant even if you never see it again or if you’ve it doesn’t even matter to you but this is relevant nitric oxide and I’ll start here saying it is one of the most powerful vasodilators known okay so vasodilation means that it takes a blood vessel that might be open this much and it opens it this much okay so there’s blood flowing through here okay and this will allow more blood to flow through okay so vasodilation allows more blood to flow through the blood vessel okay so if that’s the blood vessel all right so it’s it’s important because there are heart medications that may do this you may have heard of nitroglycerin nitroglycerin you know the little pill that some people put under their tongue when they feel like they’re having angina or something like that and that will dilate the blood vessels which will lower the blood pressure okay so it’s like if you if you if you’re trying to put a bunch of water through a hose and then you make that hose larger it relieves the pressure okay so that’s what that’s what this does that’s what vasodilation does decreases the blood pressure and that’s really important and it increases blood flow now another place that’s kind of interesting where this where this is well known is there’s

a little drug called viagra viagra which started out as a blood pressure medication because ultimately it led to increases in nitric oxide okay so it led to increases in nitric oxide and it vasodilate ‘add the trouble is viagra tended to vasodilate more in a specific region and that would cause an erection and so the the drug company who was researching this thought well that seems useful and so they made a lot of money by by making viagra and all it does is it increases nitric oxide and it causes vasodilation okay all right now here’s something else that will be asked about on exams and I’ll tell you why it’s important this is your lipid bilayer here okay so those go down and then you’ve got got those things all the way down this is a phospholipid now what happens in this case is that we want to have a signal that occurs inside the cell or we may want to release something out of the cell but we have to make it first okay so what happens sometimes is will actually take one of the tails of this phospholipid change it around a little bit through this PLA to phospholipase a2 and this is the enzyme that does it and turn it into something called arachidonic acid okay arachidonic acid sounds like spider okay and that’s because that’s where they first discovered this was they discovered it in spiders and this too is very important this arachidonic acid because it goes on to form something called prostaglandins thromboxanes and something called leukotrienes now you may never have heard of any of those I don’t know but prostaglandins cause pain fever inflammation okay certain prostaglandins do and so it would be handy if someone was suffering from pain fever and inflammation to block this okay so this arachidonic acid not let it turn into the prostaglandin and so here’s the enzyme that does that they’re called it’s called cyclooxygenase cox-1 and cox-2 so wouldn’t it be nice if we had a medication that would block that so we would not produce as much or as many of these prostaglandins and we do the next slide shows this as well and we call those insets non-steroidal anti-inflammatory drugs okay so so that’s what that’s how ibuprofen an aspirin that’s how they work they block this mechanism so the prostaglandins can’t be made and it dueces pain fever and inflammation okay so that’s that’s pretty handy I would say another thing thromboxanes this has to do with blood pressure blood clotting those kinds of things and so we also see some effects with with that it thins the blood a little bit when you take aspirin so we can take aspirin so this is this molecule is important and remember it all just comes from phospholipids phospholipids turn into this molecule called arachidonic acid and then it makes all of these things now there’s this other thing over here called leukotrienes and that’s that’s how you’re supposed to say it it’s try for three beings eenz are double bonded molecules so leukotrienes and these guys show up in the lungs okay so they might show up in other places too but but we know that know about the most because they show up in the lungs and they are affected or they play a role in asthma okay so we’re discovering more and more about this a lot of research being done on these so we’re trying to find things that will specifically block these leukotrienes especially the ones that are involved in asthma and use that as a very effective asthma treatment okay so there’s a lot of research being done on that so you can see this is just a we call that novel or different or new or something signaling molecules that deal with these lipids and their phospholipids okay and they go on to make all of these things now we’ve been we’ve known about this the the cyclooxygenase the cox blockers that that are like the ibuprofen and the other NSAIDs the block prostaglandins but this is

kind of a new a new thing and then we’ve discovered the the effects of aspirin on on blood thinning and reducing heart attacks okay so just to go over this real quickly since I already kind of went through it leukotrienes have a role in at asthma and anaphylaxis so so a large immune response that’s what anaphylaxis is in general and then the prostitutes which are the prostaglandins that I was talking about inflammation pain fever sleep I didn’t mention that thromboxanes which have their effects on they basically thin the blood and they prevent clots okay so so that’s what aspirin does the thromboxanes will promote that so if we block those then we reduce our chances of a heart attack or a stroke okay and that’s the other thing I mentioned non-steroidal anti-inflammatory drugs help prevent the inflammation by inhibiting this cyclooxygenase or cox and that’s what again i’ve already shown this but that’s what we see here in sets they block cyclooxygenase so this arachidonic acid can’t turn into these things okay okay all right so hopefully that makes sense all right so now modulation of signaling pathway so we care about specific the specificity competition and so what are we talking about we’re talking about a cell being here and there’s a receptor okay so here’s a receptor and the signaling molecule is supposed to come down and bind there but like I said we can put something there and block it or we can activate it directly okay and so it’s a competitive binding so we put something there that’s going to compete with this and it might lower the function or we put something there that actually activates it and we’re going to increase function okay so we we have a little bit of control over that and that’s what that’s what drugs tend to do okay so what I’m talking about again I mentioned this before is an agonist versus an antagonist okay so in agamous agonist is a drug usually that activates it and an antagonist is a drug usually oops that gets in the way it blocks it it doesn’t turn it off necessarily but it gets in the way so this guy can’t bind it okay so sometimes like in the case with epinephrine or epinephrine another word for epinephrine is adrenaline I could ask the question does adrenalin cause vasoconstriction or does it cause vasodilation so does it cause your blood vessels to get smaller so if this is the original size so Kazem to get smaller or does it cause them to get bigger okay and the answer is both okay it can actually do both because there could be different that’s what this says right here multiple receptors for one ligand so here’s adrenaline epinephrine same thing we call it up a nephron england calls it adrenaline and we also call it adrenaline depending on our usage but in one case this epinephrine might cause vasoconstriction might cause it to get smaller I just turned this from a cell into a into a blood vessel so now this is a blood vessel sorry about that so epinephrine could bind and cause this to constrict or vasopressin could bind or I’m sorry not vasopressin epinephrine could bind and cause it to dilate okay get larger okay so remember it’s the same drug it just has different receptors for that same drug okay or for that same in this case it’s a it’s a hormone okay neurohormone alright so and we can also as we know we can also give this we can also give this as a drug we can give a dren alone or epinephrine we can administer that okay so this is a better picture hopefully to two things one to show you a little more clearly but the other is to make sure that you know that it’s important an agonist versus an antagonist okay so picture won the primary ligand activates the receptor so if we talk about something like open Efrain or dopamine or something like that that’s the primary ligand that’s what we get that’s what we make in our body so this is the body functioning normally the ligand binds the receptor that’s the definition of a lie

and something that binds the receptor and so it binds the receptor and it causes a response okay now an agonist we could give a drug that’s not the same thing or sometimes we gives drugs that are the same thing but we can get a give a drug that’s different than the regular ligand that we produce but it still activates it okay so that is an agonist okay it a ghen eise’s or it makes it happen okay and it has a response it gives a response now this is showing the normal ligand so this is what the ligand would normally do here on the left again and it would have a response now we might take a drug a lot of schizophrenia drugs are like this that will come down and bind and do nothing okay now that’s where a lot of people miss that miss the questions on this is when you try to describe what an antagonist is and you want to say that it has the opposite effect it doesn’t have the opposite effect it has a nothing effect it simply gets in the way so let’s say the body is saying oh gosh we need to activate this receptor we need to cause a response but there’s an antagonist sitting on it we’ve taken a drug some kind of a medication that’s sitting right here and so when this guy over here tries to bind it’s rejected okay it can’t bind so the agonist activates the antagonist blocks the activation okay so it doesn’t let it react or it doesn’t let it have a response so there’s no response okay not an opposite response just no response at all okay so this is a this is a picture in case you you missed it earlier so this is if we give if we were to administer epinephrine or adrenaline we’re in America so we should call this epinephrine or at least I’m in America so this is an alpha we would call it an alpha adrenergic receptor this is a beta adrenergic receptor same ligand same thing can bind to both of these and it does it binds to both of these okay so I asked earlier what happens when you release adrenaline do you have as a dilation which we see here or do you have as a constriction I said the answer is both but it depends on where it is right because if you have an adrenaline rush you definitely want to increase blood flow to your skeletal muscles okay because you want to be able to run away if you have to but you don’t necessarily so that would be what you would see here to the skeletal muscles but you don’t necessarily want to increase blood flow to your digestion okay so that’s not the time to be digesting the cheeseburger you ate so you reduce blood flow to those areas and that’s if you think about that that’s pretty powerful you have an epinephrine or an adrenaline release and your but all you have to do is put you have one ligand epinephrine and all you have to do is put different receptors for the same ligand in different places one of them causes vasodilation one of them causes vasoconstriction okay so hopefully we went through that in good enough detail that you that you understand it so there we go