Selectivity and potency of opioid peptides in regulating human chorionic gonadotropin release from term trophoblast tissue

The in vitro effect of three opioid peptides on hCG release from term trophoblast tissue was investigated. These peptides were prototypic for opioid receptors of the following types: kappa [dynorphin(1-13)], mu (DAMGO) H-Tyr-d-Ala²-Gly-N-Me-Phe-Gly⁵-ol, and delta (DPDPE) H-Tyr-O-Pen-Gly-Phe-d-Pen-OH[d-Pen²,d-Pen⁵]enkephalin. All peptides stimulated hCG release and their concentration-response curves were bell shaped. Their order of potency was kappa ⋙ mu > delta. Stimulation of hCG release by any of the peptides was totally reversed by opioid antagonists, indicating that the action of peptides is mediated by placental opioid receptors. In order to confirm the specificity of opioid regulation of hCG release, three nonopioid drugs (cocaine, nicotine, and isoproterenol), with binding proteins and receptors known to be present in trophoblast tissue membranes, were also investigated. Stimulation of hCG release caused by certain concentrations of nonopioid drugs was not reversed by opioid antagonists, demonstrating that their effect is not mediated by opioid receptors. Furthermore, the concentration-response curve of isoproterenol was biphasic, suggesting the presence of a mechanism regulating hCG release that is not mediated by placental β-adrenergic receptors. Data presented in this manuscript indicate that placental opioid receptors mediate one of the mechanisms regulating hCG release from trophoblast tissue and confirm our earlier results using opioid drugs.