Receptors are any substance which provide specific binding site where natural substance or drugs gets attached and produce the action.
A large number of drugs act through this mechanism of action.
Most drugs are manufactured for receptor mediated action. The action produced by this mechanism is known as intrinsic activity.
Example is adrenaline gets attached to adrenergic receptor and produces the action of contraction and increased heart rate.
What you get below?
- Introduction to Receptors
- Types of Receptors
- Receptor regulation theory
- Conclusion
- Frequently Asked Questions (FAQs)
Introduction to Receptors
As we have studied in the previous many blogs of mine about receptors, about its definition and many basic things. Here we will directly start with the type of receptors are how it works in detail with diagrams.
We will further study the types of receptors in detail along with its sub-type and example so that your concept will be clear and you can crack any competitive exams like GPAT, NIPER JEE and many more.
Types of Receptors
- Ligand gated ion channels (Ionotropic receptors).
- G-protein coupled receptor (Metabotropic receptors).
- Enzymatic receptor (Tyrosinekinase).
- Receptor regulating gene expulsion (Transcription factor or steroid).
Now we will understand the types of receptor in detail.
1. Ligand gated ion channels (Ionotropic receptors)
Ligand gated ion channel is localized on the membrane.
The natural ligands like Acetylcholine or GABA or Amino acids acts by regulating trans-membrane flow of ions. All these are synaptic transmitters.
When these ligands binds to specific receptors, ion channel opens the gate and the appropriate ions flows along the concentration gradient and alters the electron potential across the membrane.
Example: Acetylcholine opens sodium channels and Glutamate opens potassium channel.
The flow of ions causes depolarization of the cell membrane.
The time of Ligand binding and cellular effect is just in milliseconds.
This is the fastest signalling system. Example: Nicotinic- Cholinergic receptor.
2) G-protein coupled receptor (Metabotropic receptors)
Membrane bound, which are coupled to effectors system through GTP binding is called as G-protein coupled receptor.
Various G-proteins are:
| G-Protein | Receptor for | Signaling pathway Effector |
| Gs | β-Adrenergic, Histaminergic receptor, Glucagon | Increase adenylyl cyclase and cyclic AMP. |
| Gi123 | α-Adrenergic and Acetylcholine | Decrease adenylyl cyclase and cyclic AMP. Open potassium channel. |
| Gq | Acetylcholine | Phospholipase-C, IP3, Cytoplasmic Calcium channel. |
| G0 | Neurotransmitters in brain | ——————— |
Many Extracellular ligands act by increasing concentration of intracellular second messenger. Example: Cyclic AMP.
Receptor binding activates G-protein which changes the activity of effector element. Resulting in change in the concentration of second messengers.
Most of the receptors in the body belong to this family.
Example: Muscarinic cholinergic receptor, Adrenergic receptor, Histaminergic receptor, Opiate Receptor and many peptide hormone.
Ligand receptor interaction lasts for milliseconds, and G-protein coupled receptor lasts for 10 seconds.
Because of this, in G-protein coupled receptor binding of only fraction of receptor population is enough to produce maximal tissue response.
Further G-protein coupled receptors are divided in four types:
- Adenylase cyclase: cAMP System.
- Phospholipase C: Inositol Phosphate system (IP3- DAG pathway).
- Cyclic GMP system.
- Regulation of ion channels.
1. Adenylase cyclase: cAMP System:
Effect produced due to this system are Ionotropic and chronotropic, Relaxation of smooth muscle, Glycogenolysis, Lipolysis.
When Ligand bind with receptor, it activates the G-protein which results in activation of adenylase cyclase, which results in intracellular accumulation of cAMP, this cAMP functions through cAMP dependent protein kinase.
These protein kinase A phosphorylates and at least the function of many enzymes, transports and structural proteins to produce contractility, impulse generation in heart, relaxation in smooth muscle, glycogenolysis, lipolysis, inhibition of secretion or mediator release and hormone synthesis.
2. Phospholipase C: Inositol Phosphate system (IP3- DAG pathway):
When Ligand binds with the receptor it promotes activation of Phospholipase C which results into hydrolysis of membrane phospholipids, that further generates secondary messenger.
The secondary messenger are IP3 (Inositol tri Phosphate) and DAG (Diacyl glycerol).
IP3 is responsible for mobilization of calcium from intracellular depots.
DAG is responsible for activation of protein kinase and this activation of protein kinase in presence of calcium ion.
Systolic calcium ion acts through Calmoduline.
This Calmoduline produces various effects like contraction, secretion, transmitter release, prostaglandin secretion, metabolism, membrane function and cellular function too.
This system is activated by Phospholipase.
3. Cyclic GMP system:
Cyclic GMP system is very common theoretically with the cAMP system i.e. Adenylyl cyclase system but just the slight difference between these two theoretically is, instead of Adenylyl cyclase enzyme here there is Guanylate cyclase enzyme.
When Ligand bind with receptor, it activates the G-protein which results in activation of Guanylate cyclase, which results in intracellular accumulation of cGMP, this cGMP functions through cGMP dependent protein kinase.
These protein kinase A phosphorylates and at least the function of many enzymes, transports and structural proteins to produce contractility, impulse generation in heart, relaxation in smooth muscle, glycogenolysis, lipolysis, inhibition of secretion or mediator release and hormone synthesis.
4. Regulation of ion channels:
G-protein can control the functioning of ion channel by not involving any secondary messengers like IP3 (Inositol tri Phosphate) and DAG (Diacyl glycerol).
It can bring about hyperpolarization, depolarization as well as change in intracellular calcium level.
Example is contraction in cardiac muscle.
3) Enzymatic receptor (Tyrosinekinase):
Also known as Enzyme linked Receptors.
These receptors are directly link to tyrosinekinase. Tyrosinekinase is a heterotetrameric Glycoprotein.
Receptor binding domain present on extracellular site (α subunit). Produce conformational changes in intracellular β subunit. Example is Insulin Receptor.
When insulin binds with α subunit, it activates tyrosine kinase present on β subunit by phosphorylation.
Ones this enzymes activates, it activates or deactivates many enzymes present in the cell.
Example: Insulin activates Glucokinase, Glycogen synthase and it inactivates process of lipolysis.
Insulin receptor is a heterotetrameric glycoprotein consists of two subunits extracellular α subunit and two transmembrane β subunit linked together with disulphide bond.
α subunit carries insulin binding site and β subunit carries tyrosine kinase activity.
When insulin binds with α subunit of receptor protein tyrosine at β subunit, this is activated by phosphorylation.
The activated tyrosine kinase act on many intracellular enzymes by phosphorylation or dephosphorylation of them. So that some enzyme are activated while some are inactivated.
Thus the insulin action is exerted on target cell by activation of certain enzyme and by inactivation of certain enzyme.
4) Receptor regulating gene expulsion (Transcription factor or steroid):
Receptor mediated regulation of DNA transcription is characterized of steroids and thyroid hormone.
These are considerable lipid soluble to cross the plasma membrane and acts on the specific intramolecular receptor. This results in stimulation of transcription of several genes.
This leads to synthesis of particular protein and production of cellular effect.
Receptors are the constituents of cytosol and nucleus.
The specificity of receptor control synthesis of specific proteins.
Example: Mineralocorticoids of transport protein (renal tubular function), Glucocorticoids of lipocortin (Anti-inflammatory activity).
Receptor regulation theory
It contains two types:
- Receptor down-regulation.
- Receptor up-regulation.
1. Receptor down-regulation:
When receptors are exposed to agonists for more time, the sensitivity of receptor towards agonist decreases. This phenomenon is known as down-regulation.
It occurs when prolonged use of agonist has taken place, this decreases the number and sensitivity of agonist towards receptors and this decreases the drug effect.
Example is use of salbutamol down regulates the beta receptors.
2. Receptor up-regulation:
When receptors are blocked for long time, the sensitivity of receptor towards agonist increases. This phenomenon is known as up-regulation. .
It occurs when prolonged use of Antagonist has taken place, this increases the number and sensitivity of agonist towards receptors and this increases the drug effect.
Example is use of propranolol is stopped after prolonged use because it produces withdrawal symptoms and rise BP rises this causes angina.
Conclusion
Here we have studied all the aspects of knowledge about the receptors in detail along with its diagrams which are important to understand. Here we also complete all the aspects of General pharmacology; this was the base for the upcoming pharmacology in the higher studies.
If you understand this, the higher things will be very easy for you. I have covered all the aspects of knowledge about the pharmacology like its definition its types like pharmacokinetics and Pharmacodynamics.
Routes of drug administration, Pharmacokinetics, Drug Absorption and Drug Distribution, Drug Metabolism and Drug Excretion, Pharmacodynamics, and Mechanism of Drug Action, all these Phenomena are explained in my previous blogs.
We have studied pharmacokinetics and Pharmacodynamics in detail and separately. Please do read my previous blogs so that you may get all the points clear.
I have also answered the most asked questions or say frequently asked questions of each and every topic we study.
If you read it carefully you will definitely get micro knowledge (in depth) about all the things.
I have also mentioned the summary part of whole blog in the conclusion section of each and every blog which have made.
Now we will study the summary of this blog in short: selectivity of drugs for receptor improves the action of drug to the site of action. Some drug may prolong the action and some may retard too.
There are four types of receptors, and they are Ionotropic receptors, Metabotropic receptors, Tyrosinekinase, Transcription factor or steroid. Each of them perform bit differently but the overall property of action is same.
Frequently Asked Questions (FAQs)
Yes, receptors can regenerate. Each and every cell can regenerate except neurons because they do not have centrioles.
Nowadays most of the drugs actions through the receptor mediated action. Receptors are important to produce the drug action.
When receptors are exposed to agonist for more time it decreases it affinity towards the receptor.
In short, the receptors provide the active site on which the drug acts and this facilitates the action.
Receptors are classified on the basis of action of drug as
1. Adenylase cyclase: cAMP System.
2. Phospholipase C: Inositol Phosphate system (IP3- DAG pathway).
3. Cyclic GMP system.
4. Regulation of ion channels.
Receptors are situated on the cell surface means plasma membrane or inside the cell surface.
Receptors are very sensitive for many factors but most importantly they are specific.
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