title: Activation of a NO-cyclic GMP system by NO donors potentiates beta-endorphin-induced antinociception in the mouse.
abstract: Nitric oxide (NO) donors such as sodium nitroprusside (SNP, 0.01-1 micrograms) or 3-morpholino-sydnonimine (SIN-1, 0.1-10 micrograms) administered intracerebroventricularly (i.c.v) produced a dose-dependent potentiation of beta-endorphin-induced antinociception assessed by the tail-flick test in ICR mice. The same i.c.v. treatment with SNP or SIN-1 did not affect the antinociception induced by mu-, delta-, or kappa-opioid receptor agonists. The goal of the present study was to determine if the potentiation of the beta-endorphin-induced antinociception by NO donors is mediated by the activation of NO-cGMP system. Co-administration of hemoglobin (30-120 micrograms) or methylene blue (1.25-5 micrograms), but not N omega-nitro-L-arginine (1-5 micrograms) given i.c.v. dose-dependently attenuated the potentiating effects of SNP or SIN-1 on beta-endorphin-induced antinociception. However, the same i.c.v. treatments of mice with hemoglobin, methylene blue or N omega-nitro-L-arginine did not directly affect the i.c.v. administered beta-endorphin-induced antinociception. On the other hand, the treatment of mice with a combination of NO donor (SNP, 0.1 micrograms or SIN-1, 1 microgram) and zaprinast (a cGMP phosphodiesterase inhibitor, 1 microgram) further potentiated beta-endorphin-induced antinociception. These results indicate that the potentiating effect of SNP or SIN-1 on beta-endorphin-induced antinociception is mediated by the increased production of NO-cyclic GMP in the brain. However, the NO-cGMP system is not directly involved in the beta-endorphin-induced antinociception.
authors.affiliation: Department of Pharmacology, Medical College of Wisconsin, Milwaukee, WI 53226, USA Department of Anesthesiology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
authors.forename: Jimmy Yu
authors.initials: JY
authors.lastname: Xu
authors.forename: Galen M
authors.initials: GM
authors.lastname: Pieper
authors.forename: Leon F
authors.initials: LF
authors.lastname: Tseng
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D006152:Cyclic GMP / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D008981:Molsidomine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000008:administration & dosage / Q000494:pharmacology; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D001615:beta-Endorphin / Q000494:pharmacology*
chemical_list: D000700:Analgesics; D000701:Analgesics, Opioid; D009599:Nitroprusside; D009569:Nitric Oxide; C002385:linsidomine; D001615:beta-Endorphin; D008981:Molsidomine; D006152:Cyclic GMP