Inhibition of cardiovascular activity following microinjection of novel opioid-like neuropeptide nociceptin (orphanin FQ) into the rat rostral ventrolateral medulla.
Nociceptin (orphanin FQ), the newly discovered endogenous ligand for the novel opioid receptor-like 1 receptor, has been initially found to participate in pain modulation. In this study, centrally mediated cardiovascular actions of this peptide were investigated in the alpha-chloralose/urethane-anesthetized rats. We found that bilateral injection of nociceptin (10 nmol) into the rostral ventrolateral medulla (RVLM), wherein injection of excitatory amino acid dl-homocysteic acid (3 nmol) induced typical pressor responses, significantly reduced arterial blood pressure and heart rate by -32% and -15%, respectively. Reduction of blood pressure and heart rate in response to intra-RVLM injection of nociceptin was dose-dependent with a threshold dose being 3 nmol. Pretreatment with the selective nociceptin receptor antagonist, [Phe1psi(CH2-NH)Gly2]NC(1-13)NH2 (10 nmol), into the RVLM abolished the nociceptin-induced cardiovascular inhibition. In contrast, non-selective opioid receptor antagonist, naloxone (10 nmol), did not modify the hypotension and bradycardia induced by nociceptin, even though naloxone at the same dose prevented reduction of blood pressure and heart rate induced by intra-RVLM injection of methionine-enkephalin (3 nmol). Both [Phe1psi(CH2-NH)Gly2]NC(1-13)NH2 and naloxone injection alone had no significant effect on baseline blood pressure and heart rate. These data suggest that the newly discovered opioid-like neuropeptide nociceptin in the CNS exert powerful influence on hemodynamic activity by affecting the RVLM neurons. This influence is inhibitory in nature, which may not be active in normal physiological conditions. Moreover, the cardiovascular effects of nociceptin were mediated by activation of specific nociceptin receptors rather than typical naloxone-sensitive opioid receptors.
Chu
X
X
Department of Physiology, Shanghai Medical University, 138 Yi Xue Yuan Road, Shanghai 200032, China.
Xu
N
N
Li
P
P
Mao
L
L
Wang
J Q
JQ
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects*; D008845:Microinjections; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D018847:Opioid Peptides / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000819:agonists*; D000097629:Nociceptin
D009270:Naloxone; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D011957:Receptors, Opioid; D000097629:Nociceptin