ENDOMORPHIN-1 AND ENDOMORPHIN-2, THE ENDOGENOUS MU-OPIOID AGONISTS, PRODUCE BIPHASIC CHANGES IN SYSTEMIC ARTERIAL-PRESSURE IN THE CAT

The endogenous peptides endomorphin 1 and 2 are newly isolated, potent , selective mu-opioid receptor agonists. In the present study, respons es to the endomorphin peptides were investigated in the systemic vascu lar bed of the cat. Endomorphin 1 and 2 induced dose-related biphasic changes in systemic arterial pressure when injected in doses of 1-30 n mol/kg i.v. The biphasic responses to endomorphin 1 and 2 were charact erized by an initial increase followed by a decrease in systemic arter ial pressure. In terms of relative vasodepressor activity, endomorphin 1 and 2 were similar in potency and approximately 10-fold less potent than the ORL1 ligand nociceptin (orphanin FQ) in decreasing systemic arterial pressure. The biphasic arterial pressure changes in response to endomorphin 1 and 2 were inhibited by the opioid receptor antagonis t naloxone in a dose of 2 mg/kg i.v. These results demonstrate that en domorphin 1 and 2 produce significant, naloxone-sensitive changes in s ystemic arterial pressure that are characterized by an initial increas e followed by a secondary decrease in arterial pressure in the cat. (C ) 1998 Elsevier Science Inc.