EXTRAORDINARY POTENCY OF A NOVEL DELTA-OPIOID RECEPTOR AGONIST IS DUEIN PART TO INCREASED EFFICACY

A new cyclic opioid peptide of sequence Tyr-D-Pen-Gly-Phe-Cys-Phe (HBP 2) was examined in the mouse isolated vas deferens (MVD) bioassay. Stu dies with receptor-selective opioid antagonists showed the peptide to be highly selective for delta opioid receptors. HBP2 and the standard delta agonist DPDPE were simultaneously compared using the technique o f partial irreversible receptor blockade; data were analyzed using the operational model of pharmacologic agonism. HBP2 was approximately 16 0 times as potent as DPDPE; estimation of the affinity and efficacy of the two peptides revealed that the potency increase was due to a 5.3- fold increase in efficacy, as well as a 37-fold increase affinity. Thi s contrasts with our previous findings with other cyclic enkephalin an alogs, in which increased affinity was achieved without a change in ap parent efficacy. Analysis of concentration-response curve shape. sugge sted in addition the possibility of heterogeneity in transduction mech anisms for MVD delta receptors.