Centrally administered nociceptin/orphanin FQ (N/OFQ) evokes bradycardia, hypotension, and diuresis in mice via activation of central N/OFQ peptide receptors.
The present studies examined the cardiovascular and renal responses produced by activation of central nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptors in conscious mice. To assess this, we examined changes in heart rate (HR), mean arterial pressure (MAP), urine output (V), urinary sodium excretion (UNaV), and free water clearance (CH(2)O) produced by acute i.c.v. injection of N/OFQ (0.03, 0.3, 1, or 3 nmol) or isotonic saline vehicle (2 mul) in conscious telemetered ICR-CD1 mice. After i.c.v. injection, N/OFQ, but not vehicle, dose dependently decreased HR and MAP and increased V. At 3 nmol, N/OFQ reduced HR [control (C), 672 +/- 23 beats/min; 20 min, 411 +/- 30 beats/min] and MAP (C, 108 +/- 4 mm Hg; 20 min, 62 +/- 6 mm Hg). In the same telemetered mice, i.c.v. N/OFQ significantly elevated V (0.65 +/- 0.03 cc/2 h) compared with levels for the vehicle-treated group (0.15 +/- 0.09 cc/2 h). Central N/OFQ/vehicle did not alter UNaV or CH(2)O. In separate studies, 2-h i.c.v. pretreatment with the NOP receptor antagonist UFP-101 ([Nphe(1),Arg(14),Lys(15)]N/OFQ-NH(2)) (10 or 30 nmol) markedly, but transiently, reduced HR but not MAP, V, UNaV, or CH(2)O. After 2-h UFP-101 (10 or 30 nmol) pretreatment, subsequent i.c.v. injection of N/OFQ (1 or 3 nmol) failed to alter cardiovascular or renal function. In contrast, in separate mice, 2-h pretreatment with N/OFQ (1 or 3 nmol) or vehicle failed to prevent the cardiodepressor and diuretic responses to a subsequent i.c.v. injection of the same dose of N/OFQ. Together, these findings demonstrate that in conscious mice, the central administration of N/OFQ evokes marked bradycardia, hypotension, and diuresis by selective activation of central NOP receptors.
Burmeister
Melissa A
MA
Department of Pharmacology and Experimental Therapeutics, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA.
Kapusta
Daniel R
DR
D000595:Amino Acid Sequence; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects* / Q000502:physiology; D004231:Diuresis / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D007276:Injections, Intraventricular; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D018847:Opioid Peptides / Q000494:pharmacology*; D011957:Receptors, Opioid / Q000187:drug effects / Q000502:physiology*; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D018847:Opioid Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C479838:(Nphe(1),Arg(14),Lys(15))N-OFQ NH(2); C000722287:Oprl1 protein, mouse