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Agonist-regulated endocytosis and desensitization of the human nociceptin receptor
Santi Spampinato1, Monica Baiula
1Department of Pharmacology, University of Bologna, Bologna, Italy. santi.spampinato@unibo.it
Abstract:
A series of nociceptin receptor ligands has been investigated in relationship to their capability to promote receptor endocytosis, desensitization (evaluated as inhibition of forskolin-stimulated cAMP production) and compensatory upregulation of adenylyl cyclase activity in CHO-K1 cells expressing the cloned human nociceptin receptor. Nociceptin (NC), [Arg14, Lys15]NC-NH2 and NNC 63-0532 (0.01 nM-10 microM) induce a concentration-dependent endocytosis and recycling of the nociceptin receptor. This mechanism contributes to maintain receptor signaling as it counteracts desensitization development and enhances a compensatory upregulation of adenyl cyclase activity. In contrast, the partial agonists [Phe1,Psi(CH2NH)Gly2]NC(1-13)-NH2, Ac-RYYRIK-NH2 and Ac-RYYRWK-NH2 (up to 100 microM) fail to induce receptor endocytosis and cause a pronounced receptor desensitization that is not influenced by monensin, a blocker of recycling of the internalized receptors.
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Drug-Receptor Interaction: Agonist
Agonists can bind to receptors in different ways. Some agonists bind directly to the receptor's active site, mimicking the endogenous ligand's action.
