Acetyl-RYYRIK-NH(2) is a highly efficacious OP(4) receptor agonist in the cardiovascular system of anesthetized rats.
Nociceptin, the endogenous ligand of the OP(4) or ORL(1) (opioid receptor-like(1)) receptor, decreases blood pressure and heart rate in anesthetized rats. Since the OP(4) receptor antagonist [Phe(1)Psi(CH(2)-NH)Gly(2)]-nociceptin(1-13)NH(2) possesses an agonistic effect in this model, we examined whether other purported OP(4) receptor antagonists, acetyl-RYYRIK-NH(2) and naloxone benzoylhydrazone, antagonize the depressant effects of nociceptin. Acetyl-RYYRIK-NH(2), like nociceptin and [Phe(1)Psi(CH(2)-NH)Gly(2)]-nociceptin(1-13)NH(2) and unlike naloxone benzoylhydrazone, decreased diastolic blood pressure and heart rate (rank order of potencies: nociceptin approximately equal to acetyl-RYYRIK-NH(2) >> [Phe(1)Psi(CH(2)-NH)Gly(2)]-nociceptin(1-13)NH(2)). The depressant effects were insensitive to the OP(1-3) receptor antagonist naloxone but diminished by naloxone benzoylhydrazone. In conclusion, the hypotensive and bradycardic effects of nociceptin in the anesthetized rat are mediated via OP(4) receptors, at which acetyl-RYYRIK-NH(2) is a highly potent and efficacious agonist.
Malinowska
B
B
Department of Experimental Physiology, Medical Academy, Mickiewicz Str. 2A, 15-230 8 Białystok, Poland.
Kozłowska
H
H
Berger
H
H
Schlicker
E
E
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002319:Cardiovascular System / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009270:Naloxone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology*; D018847:Opioid Peptides / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000819:agonists*; D014665:Vasodilator Agents / Q000494:pharmacology; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D009270:Naloxone; D009292:Narcotic Antagonists; D009842:Oligopeptides; D018847:Opioid Peptides; D011957:Receptors, Opioid; D014665:Vasodilator Agents; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C118945:acetyl-RYYRIK-NH2; C058380:naloxone benzoylhydrazone; C000722285:Oprl1 protein, rat