RECEPTORS – CLASSIFICATION

Angiotesin II

Cell membrane receptor proteins are located within the phospholipid bilayer of the cell membrane of target cells.

Binding of hormones (ie, catecholamines, peptide and protein hormones) to cell membrane receptors and formation of the hormone-receptor complex initiates a signaling cascade of intracellular events, resulting in a specific biologic response.

Protease activated receptors (PARs), a family of four seven-transmembrane G protein-coupled receptors (PAR1, PAR2, PAR3, PAR4), act as targets for signalling by various proteolytic enzymes (thrombin, trypsin). PARs are characterized by a unique activation mechanism involving the proteolytic unmasking of a tethered ligand that stimulates the receptor. They release PGE2 and this inturn protects the epithelium.

Ref: Ganong’s Review of Medical Physiology, 21st Edition, Page 667

GnRH receptors are a part of G protein coupled receptor superfamily and it functions primarily through the phospholipase C induced diacylglycerol and inositol triphosphate second messenger system.

C i.e. Adrenalin

C i.e. Corticosteroids

Classification of Hormones by Lipid/Water Solubility

A i.e. Mainly on nuclear surface

A i.e. It interacts transmembrane domain; B i.e. GTP to GDP; C i.e. Adenyl cyclase activation leads to increased cAMP

A i.e. It binds to ligands at the cell surfac

G protein coupled (linked) receptor (GPCRs)

• These cell surface receptors bind to the ligand at the cell surfaceQ. And have 7 trans membrane segments that loop in and out of the cell membraneQ. So the receptor is also k/a seven transmembrane domain (7TM) receptors, heptahelical or serpentine receptor.
• Part of receptor that protudes into cytoplasm (cytoplasmic tail of receptor) is coupled to G protein that has 3 different subunits (hetrotrimeric) – a, y. This G protein has an ability to bind guanosine nucleotides.

–                   In resting (inactive) state the a, 13, y subunits form a complex that binds GDP on

a subunitQ.

When receptor gets activated (after ligand binding) it causes this GDP bound trimeric G protein complex to associate with cytoplasmic tail of receptor and to exchange GDP by GTP. This exchange causes a subunit to dissociate

from combined fl & r subunits. This separated a subunit brings about biological effectQ. The 0 y subunits do not separate from each other and activates variety of effectors. (So dissociation of subunits 1/t action).

When ligand is removed from receptor, the intrinsic GTP ase activity of a subunit inactivates itself by converting its bound GTP into GDPQ.

In the absence of hormone, the heterotrimeric (a,13,y) G protein complex is in an inactive GDP bound form anchored to plasma membrane through prenylated groups on 13 y subunits and by myristoylated groups on a-subunit , but not associated with the receoptor. Binding of hormone (H) to receptor causes conformational change of receptor and activation of G protein complex d/t exchange of GDP with GTP on a subunit.

Tadenyl cyclase, Ca”/Na⁺ /C1- channels for a-s

–         TIC* channels for al and ao

–         T Phospholipase C[It for a_q and phospholipase CI3₂ for an

–         T C GMP phosphodiesterases for a_t and CI channel for cti2

• Depending on the coupling of ligand (hormone) to inhibitory G protein(Gi) or stimulatory G protein (Gs) receptors, these can either decrease or increase the activity of intracellular enzyme. (so it is not dependent on a subunit).
• Mechanism of action: Ligand (photon, protein, amine hormone, & neurotransmitter) binding —> conformation change & activation of G protein —> exchange of GDP for GTP and dissociation between a- and 13 y subunits which interact with effectors.
• a – subunit act on Na, Ca, K- channels and phospholipse – C (PLC). p y subunit acts on adenyl cyclase, phospholipase A2, DLC, Ca – ATPase etc.

Adenyl cyclase – cAMP pathway activation (i.e. adenyl cyclase activation lit T cAMP) causes stimulatin of cAMP dependent prtein kinase (protein kinase A) which phosphorylates the receptorQ.

G protein coupled receptor kinase are protein kinase that phosphorylates only active GPCRs Phosphorylation of receptor 1/t translocation & arrest linking.

• GPCRs are found only in eukaryotes, including yeast, plants & choanoflagellates. These are grouped in 6 classes: A (rhodopsin like); B (secretin receptor family); C (pheromone/ metabotropic glutamate); D (Fungal mating pheromone receptor); E (cyclic AMP receptor); and F (frizzled or smoothened).

Ans is ‘c’ i.e. insulin binds to a receptor molecule on the outer surface of the plasma membrane which activates the tyrosine kinase that is the cytosolic domain of the receptor.

o Insulin receptors are membrane receptor of tyrosine kinase enzyme linked type. Their hormone binding site is extracellular and effective domain (i.e. tyrosine kinase) is intracellular.

o Insulin binds at extracellular site (outer surface of plasma membrane) and this binding activates intracellular (cytoso­lic) domain, i.e., tyrosine kinase

Ans. C i.e. Beta1

Beta adrenergic receptors

• Activation of beta-1 receptors induces positive inotropic, chronotropic output of the cardiac muscle, leading to
  increased heart rate and blood pressure, secretion of ghrelin from the stomach, and renin release from the kidneys.
• Activation of beta-2 receptors induces smooth muscle relaxation in the lungs, gastrointestinal tract, uterus, and various blood vessels. Increased heart rate and heart muscle contraction is also associated with the beta-2 receptors.
• Beta-3 receptors are mainly located in adipose tissue. Activation of the beta-3 receptors induces the metabolism of lipids.

Ans. D. All of the above

Intracellular receptors are receptors located inside the cell rather than on its cell membrane. Classic hormones that use intracellular receptors include thyroid and steroid hormones. Examples are the class of nuclear receptors located in the cell nucleus and cytoplasm and the IP₃ receptor located on the endoplasmic reticulum.

Ans. is `b & c’ i.e., T3 & T4

Ans. is ‘c^‘ i.e., Glucocorticoids