0:04 hello everyone we will specify this video for illustration of adrenergic receptors before I start explaining this adrenergic receptors I want to mention two concepts the first concept I want you to know is pre-synaptic receptors versus postsynaptic receptors what does pre-synaptic and postsynaptic mean because you will hear about these terms very often while you study number two we want to discuss a term called second messenger what the second messenger mean let's start with the first concept pre-synaptic and postsynaptic consider this any nerve fiber this is the nerve
0:52 body and it's connecting to another nerve body anywhere either in CNS or prayfully if there is a receptor present here let's call it Alpha 2 or beta2 and if the same receptor is also present here Alpha 2 and beta2 remember that this attachment or the space here is called synapse which of these are called postsynaptic and which are pre-synaptic look at the direction of the chemical transmitter from where it comes and to where it goes if the chemical transmitter is moving in this direction from the sill to this one or let's assume this is a tissue instead and this is a nerve terminal and signal is moving in this direction then the receptors present
1:40 on the neuron or nerve terminal which releases the transmitter is called pre-synaptic pre because the space is called synapse and it's located before so it's pre-synaptic on the same principle the other receptors present on the cell or this tissue are called postsynaptic this is for the terms pre-ampo synaptic okay now before we dwell into details may I ask you does this presynaptic receptor has in anything to do with this tissue or its function is only about its own nerve cell its function stops in here so the spray synaptic receptor present on any nerve terminal or any neuron releasing transmitters if you say pre-synaptic then you'll mean that its only function is to
2:32 regulate the release of transmitters from this nerve terminal or this cell releasing transmitters however it has nothing to do with the tissue itself or the responder on the other hand if we say that the transmitter is released from here to here in this direction this is the receptor is called pre-synaptic and this one is a postsynaptic to avoid any confusion if you hear the term pre-synaptic receptor from now till we finish all of the lectures when you hear pre-synaptic then it means these are the receptors located at presynaptic membrane its function is to regulate
3:17 transmitters release so some of them increase others decrease as we will see now for now if you hear pre-synaptic then its function is not in the tissue but it's too regulate transmitter's release this is the first concept second one is something called second messenger naturally we will specify a huge part in general pharmacology chapter only for receptors we will discuss them in detail but for now at least you know most of the receptors are present on cell membrane if this is a cell then the receptor is here on cell membrane the receptor doesn't ever perform any function when it bind to its Agonist it can only act through something called second messenger
4:04 the second messenger might be a g protein it might be a kinase protein kinase it might be tyrosine kinase and so on or this receptor might be working through ION channel in other words there is no receptor working directly like this except for focus on this one except for only one type of receptors its activation can lead to immediate outcome do you know which one this might be let me remind you do you remember ganglia from the post video this ganglia contains acetylcholine when released it opens a gate do you remember its name this gets called nicotinic acetylcholine receptor this receptor here called nicotinic acetylcholine receptor is the only type of receptors which by its activation the gate opens resulting in sodium ion influx leading to depolarization of tissue so
4:54 the only type producing immediate outcome and acts quickly without second messenger is this type called ION channel linked receptor if you have any skill question State on this the only type of receptors that has no second messenger then it is the first type of receptors naturally we will explain all of this in detail on General chapter but for now at least you have an idea about it so it is the first type called iron Channel LinkedIn receptor except for this one any other type of receptors X through second messenger now how many types of receptors are present in your body you have four types I won't discuss them in detail now however you should know that 70 percent offers receptors in your body 70 percent of the overall number of receptors present inside
5:45 your body are something called G protein LinkedIn receptors so 70 percent of receptors inside your body are G protein linked receptors like this one we are explaining in this video which is adrenergic receptors all of the other energy receptors are G protein LinkedIn receptors [Music] don't forget this 70 percent receptors we have are G protein LinkedIn receptors acting through second messenger the second messenger might be a geoprotein protein kinase ION channel or whatever this is the second concept let's now talk about the types of adrenergic receptors and discuss them in detail in the past video physiology introduction I told you that adrenergic system
6:34 or sympathetic System main transmitter is more adrenaline or nor epinephrine and when it is released it can affect or activate five types of receptors first type is Alpha One Second times Alpha two third is beta1 fourth is beta2 and the last one is beta 3. those are the five common types of adrenergic receptors that adrenaline or noradrenaline can act on and as I told you any tissue has one type of this as predominant one it it may indeed have more than one type but only one is the predominant exert in the most Market influence let's talk about this Alpha One firstly discussing its sites functions and its second messenger which type of second messenger
7:26 this Alpha One before anything you should know that recently there is nothing called Alpha One anymore it's divided into subtypes we now have subtype a b d and there are more but only keep these three in mind Alpha 2 is divided into a b and c we can no longer say Alpha One and stop instead we say that a certain tissue has Alpha One a specifically they are slightly different from another tissue with Alpha 1D and so on the first and the most important side for this Alpha receptor is blood vessels most of blood vessels you have contain Alpha and its activation results in vasoconstriction if you want to be more scientifically exact it is one alpha a
8:15 specifically most blood vessels contain Alpha 1 a receptor its function is vasoconstriction number two is the uterus Alpha receptors in the uterus also cause contraction however it's somehow weak in there so I don't want someone to say that we can make use of this receptor to induce an abortion in a pregnant woman it does cause contraction but not so strong that it could lead to abortion consider this effect to be theoretical theoretically it can cause contraction third side is the eye he is the eye this is the pupil here is something called radial muscles that you call dilator pure Pele this is a little pupily contain Alpha One when it is activated it
9:00 leads to contraction note that alpha 1 is always causing contraction or constriction and you will see the reason when this Alpha is activated in the eye it leads to contraction of the radial muscles of the eye so the pupil dilates and when the pupil dilates it's called mydriasis as you know from physiology when someone experiences sympathetic stimulation his people must dilate for a better Vision in order to face the danger fourth site for all sound receptors this is git and this is a urinary tract let's talk about them as one in both of them we always have a hole and we always have a sphincter Alpha One if it's found in the wall then it causes relaxation and this is an exception because I told you although causes contraction if it's found in the wall of
9:51 the urinary system it also causes relaxation but in sphincters it causes contraction if you want to be more scientifically exact here in this sphincter we have Alpha One a and Alpha 1D so in this sphincter we have Alpha One a and the cause and contraction why are we saying this that's because when we discuss the drugs I'll tell you that whenever you invent a drug it's better to Target only one specific subtype why because if you want to act on blood vessels only then you should Target Alpha 1A if you want to act on sphincter you have Alpha One A and E then you should choose a drug that acts on Alpha 1D considering that this subtype is not very common
10:38 except in sphincters so if you have a patient complaining of hearing retention which one is accused of course it is the alpha receptor so we should give him Alpha blocker when we block this Alpha receptor the sphincter opens and urine come out and the post we used to do this not very far in the past but about 20 years ago when someone complained of hearing retention we used to give him Alpha blocker do you know what did these people complain of these patients who received alpha blockers complain firstly of dizziness do you know why was he dizzy it's simple as you can see when I give him Alpha blocker to block Alpha here which was responsible for sphincter contract action and urine retention this Alpha blocker I gave it to the patient was non-selective so it looked Alpha here and it did solve this problem however
11:29 it also blocked Alpha receptors and blood vessels leading to loss of vasoconstriction resulting in low blood pressure so if you are smart enough and you want to invent a drug that only acts on the sphincter without affecting blood pressure the new inventor drug that blocks only Alpha 1D why this Alpha 1D we cause its present only in sphincters blood vessels doesn't have Alpha 1D this is the progress in medicine and these are the new drugs but don't mind with their names now I only want to show you how important subtype functions can be a new subtype discovery means
12:16 that a new drug is on the way which is more selective this High selectivity decreases its side effects on other tissue these are most of the parts in your body that contain Alpha receptors there is only one place left which we don't care about that much but let's have a quick Glimpse on it anyway do you remember in the past video when I told you about sweat glands do you remember the autonomic supply of sweet glands is it sympathetic or parasympathetic yes they are supplied by sympathetic system but when I told you although they are supplied by sympathetic their transmitter is acetylcholine that's why we called the nerves applying these sweat glands sympathetic cholinergic so The receptors in this glands should respond to acetylcholine accordingly
13:07 they are not supposed to belong to this family of adrenergic receptors however some of the sweat glands especially those in the palms and forehead still obey the rule in other words they are supplied by sympathetic and their nerve endings released nor adrenaline and the responders that respond to it and make your hand and foreign so we have two types of sweet glands in our body one that's cholinergic and this is the most common all over the body and one that's adrenergic present in the forehead and the Palms because its nerve is sympathetic release another adrenaline which acts on Alpha One again if we want to enumerate the size of Alpha One receptors they are present in blood vessels causing vasoconstriction they are present in the uterus their effect is weak but
13:53 still contraction they are present and the radial muscles of the IV cause contraction but be aware of this for McQ they don't cause contraction of the pupil they indeed cause contraction but not for the pupil they cause contraction of the radial muscles of the eye they are also present in the role of git and urinary tract causing relaxation they are present in the sphincters causing contraction we are missing only one thing which you may be wondering about now [Music] in all of these places why do alpha 1 receptors cause contraction everywhere except in the role of git and urinary tract where they cause relaxation here we need to return to the concept of second messenger that I told you about at the start of the video this is explained by
14:42 second messenger regarding Alpha One if this is a sill and this is Alpha 1 receptor present on cell membrane when it's activated it activates something called G protein queue time we have three types of G protein and maybe there are more than just three as you know from biochemistry we have three types of G protein g stimulatory g inhibitory and third type is called GQ is short for query or questionable when this GQ works it increases something called inocetyl triphosphate or ip3 and when ip3 increase it increases calcium you know from physiology that this calcium is an incinerator calcium never acts for the sake of common good it's never possible for calcium to
15:27 increase causing relaxation increased calcium level in any cell if that cell was contractile it leads to contraction this is why blood vessels contract you know that when alpha one works it leads to vasoconstriction this is explained on the molecular level by these steps Alpha One activation turns on GQ increase in ip3 level which increases calcium level this increased calcium and the reason behind vasoconstriction okay so much so that when we want to induce relaxation in any tissue we use drugs I'll tell you about later they are called calcium channel blockers calcium blockers because you know that the calcium always leads to contraction but then what drives gltm urinal bladder to deviate from this rule it's suppose that the alpha activates GQ
16:15 increase in ip3 includes in calcium do you know why Joy can urinal Builder rules deviate from the rule it's very simple reason if we assume this to be a sill from git wall when calcium level is increased within the cell of git wall it opens a certain type of potassium Channel called calcium dependent potassium Channel originally increased calcium level leads to activation of a certain enzyme called don't bother with the name but anyway it's called myosin light chain kinase this myosin like chinkinis is the one causing contraction however in the whole of the git and urinary tract this enzyme is absent instead there is a
17:01 certain potassium Channel when calcium level is increased it opens this type of potassium Channel and you know what when potassium channels open this cell is somehow paralyzed this cell now is paralyzed and this paralysis in medical terms is called relaxation again if some examiner wants to intimidate you you're an oral exam like this dear student can you tell me why doesn't this Alpha have any good intentions tell him indeed it doesn't because it always cause contraction he will then ask you but why tell him because it turns on GQ and GQ increased ip3 leading to increased level of calcium if he wants to pressurize you further he would then ask
17:46 you and what does calcium do tell him it acts on enzyme called myosin lyching kinase causing contraction he would then say but I think it can cause relaxation git and urinary bladder rules tell him that this is right because the rules doesn't have this enzyme instead they have a potassium Channel called calcium dependent potassium channel that opens in response to increased calcium leading to hyperpolarization of the wall resulting in relaxation for now this is all what we need to know about this Alpha so let's start discussing alpha 2. alpha 2 is too kind that it won't take too much time I'll only tell you one word and leave you to your own devices if I tell you that most of Alpha 2 in your body more than 90 percent of this Alpha 2 distributed
18:34 in your body or pre-synaptic that's it I'm saying no more I'm leaving you to your own devices what does pre-synaptic mean it means it's present on the nerve terminal if this is a nerve terminal and this is a tissue and this is synapse does alpha 2 act on tissue or on its nerve terminal of course on the nerve terminal its function is regulatory as I told you before and this Alpha 2 is nearly always opposite of alpha one this one was far from good always contraction and so on on the other hand this one is inhibitory it decreased lower epinephrine release calming you down patience relax humans relax who in the nervous one he is the one with malfunctioning Alpha 2
19:21 and since Alpha 2 is malfunctioning then this one is releasing more than enough norepinephrine such conditions when someone complains of always feeling nervous and you want to calm him down give him a drug that activates Alpha too we invented drugs for this purpose to activate this Alpha too for example if a drug addict came to us now he has repented open the cigarette booth and he is no longer taking drugs he may come to you complaining of an anxiety and tension in this situation if you want to calm him down you tell him that instead of taking substance for relaxation stop this and I'll give you a drug that stimulates Alpha 2 receptors when I stimulate your Alpha 2 and the brain and peripheral nerves it's a pre-synaptic receptor
20:10 that decreases nor epinephrine release so you will be calmer and more relaxed this is the best use of these drugs that activates Alpha 2 and we call them selective Alpha two agonists or stimulants we have Alpha 2 and many other tissue it's also present postsynaptic but it's somehow weak I told you that more than 90 percent of them are pre-synaptic for regulator nor epinephrine release decrease in norepinephrine release okay now let's shift to betalon beta1 is the commander of the heart so that it's called cardiac beta1 its most well-known place is the heart and its activation
20:55 leads to increase all of the cardiac properties count with me from heart rate to automaticity rhythmicity contractility and so on it increases all of the cardiac properties and when you have a patient complaining of arrhythmia or tachycardia this bet alone could be responsible for this then you have to give him a beta blocker until now we don't know if it has subtypes or not let's hope to discover its subtype soon I'm sure it has subtitles but this is not important for you so Peter 1 is present in the heart not only there but it is also present in the kid D if you want to Target this beta 1 in the heart search for its subtypes and invent a drug targeting them in order to be more selective those are the most well-known places for beta1 it's present in the
21:47 kidneys and it's present in the heart this beta one is also present in liposites or adipocytes fat tissue cells however beta 3 is the predominant type there so if someone asks you whether your adipose tissue have bitter one then the answer is yes but when we talk about adipocytes or fat cells it's always the beta 3 that has the most of the effect there it is their specialty the playground of beta 3 is adipocytes if betalon is mentioned just don't forget it's present in the heart and in the kidney this is all what I want you to know now beta2 beta2 is called the kind
22:32 beta2 why the kind by the way receptor is taken number two are always kind and considerate and receptors taken number one are almost always Rogue now why are beta 2 called the coin beta2 because it's the one responsible for running this is the hero 7u when God forbid a dog chases you or while you are climbing the stairs perish the thought a habit cat runs into you in the dark this beta 2 is the one saving you on such occasions in Egypt when we Face something terrify we say that Ronin is half of their carriage and this beta2 is the one responsible for this carriage's half but why number one if I am facing a threat and I need to run away what is the first thing I need it
23:24 is skeletal muscles correct I need skeletal muscle cells so this beta2 dilates your blood vessels present in skeletal muscles to give them more blood so you can run do you know why it's because if beta 2 didn't do this Alpha One would cause vasoconstriction and this is very bad if you try to run you would have a cram however this beta2 prevent this one from affecting skeletal muscles skeletal muscles blood vessels are dilated under the effect of beta 1 not only this but do you remember when I told you that skeletal muscles have nerve endings releasing a style cooling do you remember the name of the receptor respondent for acetylcholine from the post video it's a gate called nicotinic acylcholine receptor muscular type do you remember this word this one
24:15 is supposed to be acetylcholine then what is the rule of beta2 beta 2 makes this receptor cool nicotine cell cooling receptor become more sensitive to acetylcholine why we need it to be more sensitive so we can run quickly so we can depend on our muscles this is the term that you read and wonder about its meaning this is called facilitation of the neuromuscular transmission this term means that beta2 increases blood flow to the muscles and also makes this receptor that respond to a style cooling become more sensitive resulting in a quicker and better response these are two functions within the muscles still we have a third one but before the third one let me remind
25:03 you with something you had in physiology in order for a cell to have action potential one sodium ion gets inside for exchange of one potassium ion you call this action potential and depolarization now in order for muscle to contract cause a muscular contraction shouldn't sodium get inside cells potassium get out and this process occur very rapidly so we can run but if you don't have potassium in your muscles can you run if potassium stores in muscles are low can you start running sodium get inside muscle cells cause interpolarization but it wouldn't find potassium to get out for exit change this can result in disruption of the action potential and this is the rule of beta2 receptors these beta2 receptors Drive potassium ions from blood into the
25:56 cells causing something known as potassium shift it quickly draws potassium ions from the blood and push them inside muscle cells so they have sufficient potassium stores for Action potentials facilitate muscle contraction muscle contracts quicker without fatigue they increased potassium levels in cells but they decreased its level in the blood resulting in hypokalemia potassium is not sufficient in the blood be careful not to mix these effects with each other I want you to understand when I tell you how does beta 2 affect potassium if you say it causes hypokalemia you're right although it didn't mean to cause hypokalemia beta 2 didn't intend to cause hypokalemia
26:41 specifically it only intends to increase potassium ions inside the muscles so it draws them from Blood In other words beta 2 had good intentions it only wanted to facilitate muscle contraction but it didn't intend to cause hypokalemia these are three effects on the level of muscles it increases blood flow it facilitates neuromuscular transmission and it draws potassium from blood into the muscles causing hypokalemia not only this but you know that when we are running we need our heart right heart rate is increased and this beta 1 supposed to increase contractility this beta2 helps beta 1 through coronary dilocation dilation of the coronary artery so its causing dilatation in two places skeletal muscle blood vessels and coronary arteries both of them you
27:30 need during running these two places has nothing to do with Alpha for now during running skeletal muscles and Corners are under beta 2 controlled which causes vasodilation we didn't finish it while you are running you need to paint so what do you think happened to broncoi do you think they constrict you will die then beta 2 causes bronchodilatation so you can breathe easily during running [Music] and when you run don't you need high blood sugar so you can think a muscle can contract where can you give the sugar from from the liver liver is stored in sugar in the
28:17 form called glycogen okay this beta2 dissolves some of this July cushion releasing glucose into blood to enhance muscle performance and cognition function so you can react you can decide how to escape from this dog which root is the best sugar helps you in this count with me all of these functions I don't memorize them so let's try to remember them together it has three effects on muscles it causes vasodilation of skeletal muscles blood vessels and it cause facilitation of neuromuscular transmission resulting bitter muscular performance and it increased potassium stores inside muscles from where does it come from blood number four it increases blood glucose level from where from liver hell or is analysis number five it cause bronchodilatation
29:05 so you can take good breaths while you're out number six while you run air pressure can affect the eye if you are running quickly air pressure is increased on the eyes [Music] let's assume this is an eye this is cornea and this is scalero this is front image this is the iris this is a lens this is suspensory ligament of the lens this is a ciliary body anchoroid here is something called ciliary epithelium this ciliary epithelium which has beta-2 receptor it's responsible for secretion of the fluid inside your eye which preserves intraocular attention URI contain fluid in the interior and posterior Chambers both of
29:52 them are filled with fluid cooled aqueous humor where does it come from from epithelium line and ciliary body called ciliary epithelium it has beta-2 responsible for secretion of this fluid what does this have to do with running while you run air pressure on the ice is increased and we cannot live discontinue here are pressure sensors they sense the pressure once they feel increased air pressure they activate B tattoo receptor to increase equals human secretion it doesn't intend to harm you with increasing equals humor but to confront this increase in the air pressure during running now you stop and air pressure is back to normal then this equals humor is absorbed and drained through something called angle of the eye to Canal of Islam to the episcular veins and
30:38 lymphatics that's okay all of this and we didn't deviate from the word running running is half of the carriage this beta 2 is the hero responsible for this Carriage okay is there anything else yes there is something else imagine if you have a pregnant woman in your clinic who was unable to conceive for many years 15 years or so then she finally was able to get pregnant now she's praying for God every day and doing charity because she's now pregnant imagine if this brilliant woman is being chased by a stray dog what a nurse at this if she was frightened and ran away she would likely have an abortion that's why God's blessing her with B tattoo receptors in the uterus do you remember when I told you that uterusalem but it's effects on remarkable on the other hand the tattoo
31:26 effect on the uterus is Extreme really powerful it causes you to rain relaxation during danger to avoid abortion do you get it now why we are calling this kind B tattoo receptor so be careful during exams as some examiner may try to deceive you and ask you do you know a drug that can block beta-2 receptor tell him I can understand if you want a drug block on all types of receptors together but why Peter 2 specifically it didn't do anything bad maybe the only answerable effect of it is when it improves muscle contraction by facilitation of the neuromuscular Transmission in order to improve performance it might sometimes cause handshake this facilitation can sometimes result in this Chic which we call tremors this may be the only undesirable effect of beta2
32:13 sometimes people can complain to you of hand shaking especially those working in a shooting range these people may complain of shaky hands during targeting tell him it's because of beta 2 in your hands it's slightly overactive in your hands during their facilitation of the neuromuscular transmission and this is what causes these Tremors this is the only answerable effect and I can prescribe a beta blocker in this situation to remove these trimmers if this man wants to cheat he may have a shooting test and he wants a steady hands during this test give him a bit of looker blocking beta receptors which causes this Tremor so his hand Can Be steady and he can pass so all in all beta 2 is always kind and doesn't mean to cause any harm
32:59 except for these trimmers this is a very simple effect now we only have beta 3 left and you already know something about it by the way this beta 3 could be considered a different type of beta 2 is scientifically considered as a subtitle of beta2 however it's present in the Edibles tissue causing lipolysis melting the fat needless to say once you hear that it melts the fat people who are watching this video right now will say that's it we have found it you are thinking about weight loss aren't you this is good you have a sound mind and you are trying to make good application of signs however allow me to destroy your happiness why because if beta 3 had been uniformly distributed all over your fat if it had been present in the fat of my face hence all of my body evenly I would have invented a drug stimulating it causing lipolysis allowing us to
33:50 get rid of this fat without much effort but sadly enough this beta 3 receptors are present more in the upper half of the body they are present more in the face hands but they are not present in the belly fat accordingly if you stimulate beta3 receptors certain area of your body lose fat but other areas don't your face would be thinner but your belly fat will dream in the sea that's why we couldn't make much benefit from them so if you see a question in exam asking why don't we have beta 3 agonists as this receptor are supposed to induce lipolysis so why don't we have a beta 3 against among drugs treating obesity pick this peculiar sentence from the choices because it is not evenly distributed throughout the body this is the answer there is only one last concept
34:39 before we end this video I told you that Alpha One Second messenger is which type of messenger I told you that Alpha on Activision turns on a protein called GQ do you remember all types of beta receptors when they are activated they turn on the same second messenger called cyclic amb when cyclic amp is increased inside sales it causes all of these effects which we discussed so why don't they all have the same function why are beta 1 2 and 3 though in different functions it's because when cyclic amb is increased it activates other subcellular components other Kinesis kinase here is different from the one here and here again so you don't miss this concept if someone asks you what type are beta receptors present in your body tell him G protein LinkedIn receptors but how does
35:29 this beta receptor function tell him it increases cyclic amp inside cells but then why beton receptors in the heart increase contractility while betatuku's relaxation although both of them increase their theme cyclic MP tell him it is not all about cyclic amb but what's present behind this cyclic amb when cyclic amp is increased and the harder it activates a certain protein kinase which is a different from the kinase present in the cells that are under the effect of bit data 3 so it's not all about the receptor it's not all about G protein however it's all about further enzymes final effectors at the subcerial level remember this so no one can trap you during oral exams now we have finished the main Concepts about adrenergic receptors see you in the next video
