Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay, in today's episode, I will be starting with a sort of revision of GPCR, well, truly speaking, there is also added information to the topic, hence revision with addition is the motto, In the starting of episode, I will be introducing a new name for these receptors namely Metabotropic receptors. Then starting with the diagrammatic depiction and sound basis of the mechanism, I will be telling you all that G proteins are coupled with effectors like enzymes etc. GPCRs are composed of 7 transmembrane helices with an extracellular domain as drug binding site and an intracellular domain coupled to G protein, which are heterotrimeric in nature, written as alpha-beta-gamma subunit. Further alpha subunit varieties make these distinct, Gs, Gi, Gq. They have their distinct activities. When GPCR is in resting state, GDP is bound to alpha subunit. When an agonist binds, exchange of GTP for GDP occurs, then beta-gamma subunit dissociates from this, alpha GTP complex finally interacts with the target protein and activates it. That was all a quick revision of diagram and starting mechanism of GPCR, hope it helped you all with all added information, till next episode, do follow me here, stay tuned, do rate and review on ITunes, Apple podcasts, thank you!!

Welcome all to IS PHARMACOLOGY DIFFICULT Podcast ! I am Dr Radhika Vijay, in today's episode, I will be doing the last effector pathway for the functioning of GPCR, how does it actually happen, lets talk about this. The activated G proteins can open or close ion channels specific for Calcium or Potassium channels. This can occur without intervention of any second messenger like cAMP or IP3. This is achieved by hyperpolarisation or depolarisation or changes in intracellular Calcium ion concentration. Then Gs can open Calcium ion channels, Gi or Go can open Potassium ion channels, inhibit neuronal calcium ion channels. Another way is direct channel regulation, which is done by beta-gamma dimer dissociated from G protein. In this way, no component goes in vain and contributes to one or the other function through G protein receptor. With all these mechanisms, physiological responses like inotropy, chronotropy, transmitter release, etc follow to finally produce an effect! Next, I will be giving a list of receptors under different heads for each of the effector pathway of GPCR, but that being little lengthy will go with a little speed, as this wagon coach runs speedily, it will be subjected to brakes only on completion of the list. I expect all of you to write along with me or listen attentively and patiently, and if missed, opt to rewind and relisten.... Hoping a great, safe weekend time for all you my dear audience, till next episode, do follow me here, rate and review on ITunes, Apple podcasts, thank you!!

Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay, in today's episode, I will be verbally putting up my thoughts about more details on my last topic about the second effector pathway of GPCR, namely Phospholipase C:IP3-DAG Pathway. As PKc phosphorylates  many intracellular proteins and leads to various physiological responses, it all serves signalling functions. Cytosolic calcium stays low in whole of this event, this is achieved by specific pumps located at plasma membrane and endoplasmic reticulum. Next, IP3 triggers release of Calcium, which serves as a third messenger! This calcium acts as highly versatile regulator through calmodulin (CAM) and PKc. Further many varied responses can be produced at a lot of  different sites. Lastly I will discuss most importantly the termination of the effector pathways , with the development of IP3 and DAG. Before I signature today's episode and crispy communications, a little short note about intracellular calcium release, a really short information that would maintain the zest of the session. Till the next episode, do follow me here, stay tuned, do rate and review on ITunes, Apple podcasts, thank you!!

Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay, in today's episode, I will be telling you about second effector pathway of GPCR , it is named as Phospholipase C:IP3 DAG Pathway. As we dive deeper into this talk of the day, Let me start with the basic stepwise mechanism of this pathway, and that all be the content of today's episode. Activation of PLC beta by the activated GTP carrying alpha subunit of Gq leads to hydrolysis of membrane phospholipid PIP2. This process leads to the generation of second messengers IP3 and DAG. IP3 is water soluble, diffuses to the cytosol, mobilises calcium from endoplasmic reticular depots while DAG is lipophilic, remains within the membrane, and recruits Protein kinase C, which in turn is activated with the help of Calcium. Next, activated PKc phosphorylates many intracellular proteins. This last process depends on type of effector cells, finally it leads to mediation of various physiological responses. This is the main mechanism discussed for today, I will be brilliantly summarizing it so that you actually catch the depth of it really nice! Hope it works for the handful of effort done to touch the subject core for the great Wednesday, hope you all liked it, till next episode, do follow me here, stay tuned, do rate and review on ITunes, Apple podcasts, thank you!!

Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay, in today's episode, I will limit my talks in a short crispy description about cGMP(cyclic GMP) as a second messenger. cGMP is an intracellular second messenger in a limited number of tissues, like vascular smooth muscle, intestinal mucosal cell and kidney, where it respectively serves to perform actions like smooth muscle relaxation, inhibition of salt and water absorption in mucosal cell, in kidney it mediates natriuresis in kidney. Two principal forms of guanylyl cyclases(GC). In turn cGMP is generated. cGMP has two isoforms , one being bound to cell membrane and the other as cytosolic form, none is regulated by GPCR. Cell membrane bound guanylyl cyclase is regulated by transmembrane enzyme linked receptor for ANP. Cytosolic one is activated by NO. After generation by endothelial cells, NO diffuses in adjacent smooth muscles cells, stimulates guanylyl cyclase. increased cGMP, dephosphorylates MLCK, induces relaxation. This pathway is utilised by drug like sodium nitroprusside. Well that was all dear listeners, hope I am able to feed your ears with the right flow of knowledge waves, information and facts, hope you all like this session, short, but important, till next episode, do follow me here, stay tuned, do rate and review on Ituned, Apple podcast, thank you!!

Welcome to IS PHARMACOLOGY DIFFICULT Podcast ! I am Dr Radhika Vijay, in today's episode, I will be talking about first of three major Effector pathways through which GPCRs function. It is named as Adenylyl cyclase:cAMP pathway. First step is activation of adenylyl cyclase, it leads to intracellular accumulation of cyclic AMP. After this, cAMP functions through cAMP dependent protein kinase(PKa) . PKa phosphorylates many ion channels, enzymes, etc and leads to lot of manifestations or activities which you will be listening in these episode nicely..This phosphorylation and alteration activities, I will tell you more about this pathway, cAMP in addition opens a specific membrane calcium channel diretly, it is known as Cyclic Nucleotide Gated Channel(CNG). Other mediators of cellular action of Cyclic AMP are, first, Cyclic AMP Response Element Binding Protein(CREB), second one Cyclic AMP regulated guanine nucleotide exchange factors known as EPACs.The action of cAMP is terminated intracellularly by Phosphodiesterase (PDEs), it is hydrolysed to 5-AMP, various isoforms are also known PDE3, PDE4, one rare form is PDE5 which is cyclic GMP specific, You want to now more about cGMP, Well! wait for the next episode, till then do follow me here, do rate and review on ITunes, Apple podcast, stay tuned, stay safe, and happy , Thank you!!

Welcome all to IS PHARMACOLOGY DIFFICULT Podcast ! I am Dr Radhika Vijay, in today's episode I will telling you about G-Protein Coupled Receptors (GPCRs). They belong to large family of cell membrane receptors. They are found on effectors like enzymes, channels and transporters through GTP activated proteins (G Proteins). Finally they lead to response generation. Diagrammatically, GPCR is a membrane spanning heptahelical molecule, there are 3 extracellular and 3 intracellular loops. Agonist binding site lies in between helices near the extracellular face. Intracellular end binds G Proteins, where they are floating and have a domain in the cytosol. GPCR are heterotrimeric in composition, possess alpha, beta and gamma subunits. Whenever activated, alpha subunit detaches from rest two, it also has GTPase activity, GDP is displaced with GTP. The dissociated alpha subunit activates or inhibits the effector. Beta and gamma subunits also perform some function. There are different G Proteins on the basis of alpha subunits, Gs, Gi, Go, Gq. One receptor can utilise more than one G Protein, this is known as "Agonist Pleotropy". Then I will give many examples as an evidence of this characteristic. A receptor can utilise different biochemical pathways in different tissues. Then next I will throw light on detailed mechanism of action of GPCR via different subunits, time essence of the activated/inhibited state etc. Telling everything stepwise, slowly, organised manner, I will talk about Regulator of G Protein signalling (RGS). With this important information, I will halt my conversation for the episode, till next parcel of talks in continuation of this session, do follow me here, do rate and review on ITunes, Apple podcasts, stay tuned, stay enlightened, thank you!!

Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay, in today's episode, I will be conversing about Action Effect Sequence of Drugs in Pharmacodynamics. First of all, for your utter kind information, I want to tell you that Drug action and Drug effect are not synonymous. Drug action is the binding of drug to receptor and bringing about a conformational change, while on the other hand, Drug effect is the final biological response produced due to drug action occurring through a series of events in a stepwise organised manner. Hence to know more for one's knowledge, one should know that Receptor serves two important functions, firstly binding of the drug or ligand molecule after its specific identification, and secondly bringing about a final response after a conformational change. So all in all, we get to know that receptor has one ligand binding domain and another important one is effector domain. Then next I will tell you that there are 5 major categories or pathways of transducer mechanisms through which a receptor drug combo acts and produces response. Before this I will depict in my words a beautiful and simple diagram of a receptor which has external binding sites for agonist, competitive and non competitive antagonist, on inner side there is attached a transducer mechanism and finally connected to effector system leading to the response production. With all these important elaborate information, I will wind up today's episode, till next one do follow me here, stay tuned, do rate and review on ITunes, Apple podcasts, thank you!!

Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay, in today's episode I will be covering details about receptors more, specifically RECEPTOR SUBTYPES. Starting with examples for receptors of acetylcholine, namely Muscarinic (M), Nicotinic (N) receptors. These findings were confirmed with help of blockers. Ahlquist divided adrenergic receptors into alpha and beta based on different potencies of agonists. These all receptors are further subdivided in many subdivisions. There are multiple subtypes of receptors for all transmitters, hormones, etc. Receptor classification provides sound basis for different actions of closely related drugs. There are many criterias for subdivisions of drugs. First one is classical and old criteria , the Pharmacological criteria. Second criteria is Tissue distribution, which was confirmed with selective agonist and antagonists and molecular cloning. Third criteria is Ligand binding. Autoradiography has helped in mapping distribution of receptors in brain and many other organs. Fourth criteria is Transducer mechanism. Fifth and last on the list criteria is Molecular cloning. All the criterias are well accompanied with potent, apt, sufficiently important examples of many important different receptors and subtypes. Before calling it off for this episode, I will talk about Silent receptors. What is their essence and why they are named so, is their special classification justified, Please comment and let me know your opinion too, till next talkable talks, do follow me here, stay  tuned, do rate and review on Itunes , Apple podcasts, Thank you!!

Welcome all to IS PHARMACOLOGY DIFFICULT Podcast! I am Dr Radhika Vijay, in today's episode, I will go ahead by leaps and bounds to describe an introductory remark about the nature of receptors.Receptors are regulatory macromolecules, mostly proteins, some nucleic acids are also receptors. Numerous receptors amino acid sequence has been worked out and configuration plays an important role in sub classifying receptors. Basically, protein structures float in lipid membranes and there is interaction of lipophilic and hydrophilic domains among solvent molecules.It gives a look of water on one side and lipid on another side.A small ligand binds to receptor, alters charge distribution and brings about a change in equilibrium. Sometimes a conformational change is produced at a distant site too. Agonist binds and brings about change in different subunits of the receptor. Some new receptors may have no physiological ligands. Some receptors have no endogenous mediators or ligands , they are known as Orphan receptors.With a heartfelt prayer for each and everyone as the pandemic is posing new challenges everyday, I wish God showers all the peace and compassion for every ripped off soul, with the positive hope, thought and vibe, I will wind up my talk, call it for a day, till next set of chit chats, do follow me here, stay tuned, do rate and review on ITunes, Apple podcasts, stay safe and sound, do stay at home, thank you!!