Differential desensitization of human delta-opioid receptors by peptide and alkaloid agonists

The efficacy of different opioid agonists to induce acute desensitization o f 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 agoni st, caused 50% desensitization after a 30-min incubation, the same treatmen t in the presence of the selective peptide agonists, DPDPE ([D-Pen(2),D-Pen (5)]enkephalin) and deltorphin I (Tyr-D-Ala-Phe-Asp-Val-Val-Gly), almost to tally desensitized the delta-opioid receptor-mediated inhibition of adenyly l cyclase. When SK-N-BE cells were prechallenged either with alkaloid or pe ptide agonist, we observed a cross-desensitization that was less marked whe n cells were pretreated with peptide agonists and then challenged with etor phine. Taken together, these results demonstrate that human delta-opioid re ceptors are differentially desensitized by alkaloid and peptide agonists. ( C) 1999 Elsevier Science B.V. All rights reserved.