Agonists receptor down-regulation

Adrenergic receptor 2 Amino acid variants appear to be associated with receptor function and agonist induced down regulation. Some variants may predispose to some types of asthma and modulate action of (3-2-adrenergic drugs. 

Buckholtz NS, Zhou DF, Freedman DX. (1988). Serotonin2 agonist administration down-regulates rat brain serotonin2 receptors. Life Sci. 42(24) 2439-45. 

Receptor down-regulation is a phenomenon whereby an agonist, after binding to a receptor, acmally induces a decrease in the number of those receptors available for binding. Receptor up-regulation is the opposite and involves an agonist-induced increase in the number of receptors. 

Receptor down-regulation describes a slower, more prolonged process in which the actual number of available receptors is diminished.30,33 Although the exact mechanisms responsible for down-regulation are not fully understood, it appears that prolonged exposure of the agonist causes increased receptor removal, decreased receptor synthesis, or a combination of... 

Williams BR, Barber R, Clark RB. Kinetic analysis of agonist-induced down regulation of the beta(2)-adrenergic receptor in BEAS-2B cells reveals high- and low-affinity components. Mol Pharmacol 2000 58(2) 421-30. 

Chronic clozapine treatment reduces 5-HT receptor densities in the neocortex without affecting striatal Dg receptor densities, emphasizing its preferential interaction with the 5-HT receptor in vivo (586). 5-HT receptor down-regulation is produced by S-HTgA agonists as well as antagonists like clozapine. 

A. Green, Adenosine receptor down-regulation and insulin resistance following prolonged incubation of adipocytes with an Al adenosine receptor agonist, J. Biol. Chem., 1987, 262, 15702-15707. 

Chronic exposure to /I -THC and other cannabinoid receptor agonists generally leads to biological adaptive mechanisms that may be related to the phenomenon of tolerance. Cellular modifications in response to chronic agonist stimulation have included cannabinoid receptor down-regulation, as well as desensitization of signal transduction pathways. These effects have been recently reviewed in detail (Sim-Selley 2003). 

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