RECEPTORS – CLASSIFICATION

Receptors – Introduction:

• Binding sites of drug with functional correlation.

Classification of receptors:

• 4 types – Based on signal transduction mechanisms.
  • G-protein coupled receptors (metabotropic receptors)
  • Inotropic receptors
  • Enzymatic receptors
  • Intracellular receptors

1. G-protein coupled receptors:

• Also referred as “metabotropic receptors”.

Structure:

• Heptahelical (serpentine) receptors.
• Have seven transmembrane spanning segments.

MOA:

• Drugs bind to receptor –> Inturn activates G-protein (GTP activated protein).
  • G-proteins consist of three subunits – α, ß, and γ.
• G-protein is inactive – When all 3 are joined together (along with GDP).
  • When GTP replaces GDP –> α-subunit separates from ß-γ subunit –> becomes activated.
  • Reunion of α-unit: By intrinsic GTPase activity –> alpha subunit reunites with ß-γ subunits –> cycle continues.

Receptor actions:

Activated α-subunit causes 3 main effects:

• Activation (by Gs) or inhibition (by Gi) of adenyl cyclase enzyme:
  • Changes cAMP concentration.
  • cAMP concentration acts by activating protein kinases (protein kinase A).
  • Protein kinase A produces phosphorylation of their substrates.
  • Eg: ß-receptors – By increasing cAMP & Somatostatin – By decreasing cAMP.
• Activation of phospholipase C (by Gq):
  • Phospholipase C enzyme converts PIP2 to IP & DAG.
  • IP & DAG increases intracellular calcium.
  • Eg: α-receptors & vasopressin V1 receptors.
• Stimulation or inhibition of ion channels:
  • Eg. M2 receptors of ACh.

• Cyclic AMP, IP3 & DAG – Act as second messengers.
• Calcium – Acts as third messenger.

2. Inotropic receptors:

• Fastest-acting receptors.
• Drug binds directly to receptor located on an ion channel without G-protein mediation.
• Includes GABA–A, N_N, N_M, NMDA (glutamate receptors) & 5-HT3 receptors.

 

2. Enzymatic receptors:

• Have 2 sites – 
  • Extracellular & intracellular sites
• Drug binds to extracellular site.
• Intracellular site has enzymatic activity (mostly tyrosine kinase).
  • TK activated via JAK-STAT pathway.
• Seen with Insulin, GH, Prolactin & cytokines.

 

4. Intracellular receptors:

• Slowest acting receptors.
• Present in cytoplasm/nucleus.
  • In cytoplasm – Mainly glucocorticoids, mineralocorticoids & vit. D.
  • In nucleus – Mainly T3 , T4 , Retinoic acid, PPAR, estrogen, progesterone & testosterone.
• MOA: Both act by nuclear mechanisms – By affecting transcription.

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