Differential desensitization of human delta-opioid receptors by peptide and alkaloid agonists.
The efficacy of different opioid agonists to induce acute desensitization of the human delta-opioid receptor-mediated inhibition of cAMP accumulation was investigated in the neuroblastoma cell line SK-N-BE, which endogenously expresses these receptors. While etorphine, a non-selective alkaloid agonist, caused 50% desensitization after a 30-min incubation, the same treatment in the presence of the selective peptide agonists, DPDPE ([D-Pen2,D-Pen5]enkephalin) and deltorphin I (Tyr-D-Ala-Phe-Asp-Val-Val-Gly), almost totally desensitized the delta-opioid receptor-mediated inhibition of adenylyl cyclase. When SK-N-BE cells were prechallenged either with alkaloid or peptide agonist, we observed a cross-desensitization that was less marked when cells were pretreated with peptide agonists and then challenged with etorphine. Taken together, these results demonstrate that human delta-opioid receptors are differentially desensitized by alkaloid and peptide agonists.
Allouche
S
S
Laboratory of Biochemistry A, University of Caen, C.H.U. Côte de Nacre, France.
Roussel
M
M
Marie
N
N
Jauzac
P
P
D000067956:Adenylyl Cyclase Inhibitors; D000470:Alkaloids / Q000494:pharmacology; D000700:Analgesics / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism*; D004347:Drug Interactions; D020881:Enkephalin, D-Penicillamine (2,5)-; D004745:Enkephalins / Q000494:pharmacology; D005048:Etorphine / Q000494:pharmacology; D006801:Humans; D009270:Naloxone / Q000494:pharmacology; D009447:Neuroblastoma / Q000201:enzymology* / Q000235:genetics; D009842:Oligopeptides / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D000067956:Adenylyl Cyclase Inhibitors; D000470:Alkaloids; D000700:Analgesics; D000701:Analgesics, Opioid; D004745:Enkephalins; D009842:Oligopeptides; D010455:Peptides; D017465:Receptors, Opioid, delta; C060208:deltorphin I, Ala(2)-; D009270:Naloxone; D005048:Etorphine; D020881:Enkephalin, D-Penicillamine (2,5)-; D000242:Cyclic AMP