RECEPTORS – CLASSIFICATION

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.
Note:
  • 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 GABAA, NN, NM, 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.

Exam Important

  • G-protein coupled receptors are also referred as “metabotropic receptors”.
  • G-protein coupled receptors have seven transmembrane spanning segments.
  • Phospholipase C enzyme converts PIP2 to IP & DAG.
  • Cyclic AMP, IP3 & DAG act as second messengers.
  • Calcium acts as third messenger.
  • Inotropic receptors are fastest-acting receptors. 
  • Inotropic receptors are GABAA, NN, NM, NMDA (glutamate receptors) & 5-HT3 receptors.
  • Enzymatic receptors are most prevalent with insulin, GH, Prolactin & cytokines.
  • Drug binds to extracellular site of enzymatic type of receptors.
  • Intracellular site has enzymatic activity (mostly tyrosine kinase) ienzymatic type of receptors.
  • TK is activated via JAK-STAT pathway.
  •  Intracellular receptors are slowest acting receptors.
  • Glucocorticoids, mineralocorticoids & vit. D act mainly via intracellular receptors in cytoplasm.
  • T3 , T4 , Retinoic acid, PPAR, estrogen, progesterone & testosterone acts mainly via intracellular receptors in nucleus.
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