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

Abstract

The efficacy of different opioid agonists to induce acute desensitization of the human δ-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-Pen 2, d-Pen 5]enkephalin) and deltorphin I (Tyr- d-Ala-Phe-Asp-Val-Val-Gly), almost totally desensitized the δ-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 δ-opioid receptors are differentially desensitized by alkaloid and peptide agonists.