title: Evidence that nitric oxide stimulates feeding in the marsupial Sminthopsis crassicaudata.
abstract: Nitric oxide (NO) synthase inhibitors reduce food intake in rodents and chickens, suggesting that NO may stimulate feeding. We used two competitive, non-selective inhibitors of NO synthase (NOS), (NG-monomethyl-L-arginine ester [L-NMMA] and NG-nitro-L-arginine methyl ester [L-NAME]), to evaluate the role of NO mechanisms in the control of food intake in a marsupial model previously used in studies of appetite regulation. Adult male Sminthopsis crassicaudata (n = 11-16, 15 +/- 0.3 g, mean +/- S.E.M.) received L-NMMA (50, 100, 200 and 1000 mg/kg), L-NAME (50, 100 and 200 mg/kg), L-arginine (L-arg) the precursor of NO (1000 and 2000 mg/kg), L-NAME (200 mg/kg) in combination with L-arg (2000 mg/kg), or saline (0.9%). All drugs were administered intraperitoneally after 24 h of food deprivation, after which food was immediately made available ad libitum. Food intake was measured 0, 0.5, 1, 2, 4 and 24 h after treatments. In addition, we studied the effect of acute L-NAME administration on hypothalamic, cortical, hepatic and cardiac NOS activity by quantifying citrulline production. L-NMMA (1000 mg/kg) and L-NAME (100 and 200 mg/kg) suppressed food intake by 25%, 21%, and 30%, respectively, over 24 h after treatments (P < 0.05). L-arg (1000 and 2000 mg/kg) by itself had no significant effect on food intake when compared with saline (P > 0.05). When administered in combination with L-NAME (200 mg/kg), L-arg (2000 mg/kg) reversed L-NAME induced suppression of appetite (P> 0.05). Furthermore, L-NAME (200 mg/kg) significantly decreased hypothalamic (P < 0.01), cortical (P < 0.01) and hepatic (P < 0.03) NOS activity. L-NAME had no effect on cardiac NOS activity (P> 0.05). These data show that peripheral administration of L-NAME has a significant central effect, particularly in brain areas involved in appetite regulation, and suggest in marsupials, as in other mammals and birds, that NO plays a role in the regulation of food intake.
authors.affiliation: Department of Medicine, Royal Adelaide Hospital, Australia.
authors.forename: R
authors.initials: R
authors.lastname: Vozzo
authors.forename: G A
authors.initials: GA
authors.lastname: Wittert
authors.forename: I M
authors.initials: IM
authors.lastname: Chapman
authors.forename: R
authors.initials: R
authors.lastname: Fraser
authors.forename: P J
authors.initials: PJ
authors.lastname: Hope
authors.forename: M
authors.initials: M
authors.lastname: Horowitz
authors.forename: M M
authors.initials: MM
authors.lastname: Alshaher
authors.forename: V B
authors.initials: VB
authors.lastname: Kumar
authors.forename: J E
authors.initials: JE
authors.lastname: Morley
mesh_terms: D000818:Animals; D005247:Feeding Behavior / Q000502:physiology*; D008297:Male; D008394:Marsupialia / Q000502:physiology*; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester