Question

Propose different mechanisms that could contribute to the regulation of the activity of a receptor. Use Schema and explicit supporting legend.

Answer 1

Receptor is defined as a macromolecule or binding site located on cell surface or inside the effector cell that serves to recognize the signal molecule/drug and initiate the response to it, but itself has no other function. Eg. G-protein coupled receptor.

Receptor Regulation
Receptors exist in a dynamic state;
Their density and efficacy is subject to regulation by
the level of ongoing activity,
feedback from their own signal output,
other physiopathological influences.

Up regulation/ supersensitivity of receptors:
In tonically active systems, prolonged deprivation of agonist (by denervation or antagonist) results in supersensitivity of the receptor as well as to effector system to the agonist.
This is due to upregulatiopn of receptors
The mechanism involved may be unmasking of receptors or their proliferation or accentuation of signal amplification by transducer
Upregulation of receptors may be responsible for rebound hypertension after withdrawal of adrenoceptor blockers.

Down regulation of receptors
Continued exposure to an agonist or intense receptor stimulation causes desensitization or refractoriness:
receptor become less sensitive to the agonist. This is due to downregulation of receptors
This may be a reason for tachyphylaxis.
Eg. Bronchial asthma patients treated continuously with beta adrenergic agonists and parkinsonian patients treated with high doses of levodopa.

Causes:
1.Masking or internalization of the receptors
it becomes inaccessible to the agonist
2.Decreased synthesis or increased destruction of the receptors (down regulation)
Downregulation exhibited by tyrosine protein kinase receptors, α and β adrenoceptors