Evidence that nitric oxide stimulates feeding in the marsupial Sminthopsis crassicaudata

被引:17
作者
Vozzo, R
Wittert, GA
Chapman, IM
Fraser, R
Hope, PJ
Horowitz, M
Alshaher, MM
Kumar, VB
Morley, JE
机构
[1] Royal Adelaide Hosp, Dept Med, Adelaide, SA 5000, Australia
[2] St Louis Univ, Ctr Hlth, Div Geriatr Med, St Louis, MO 63104 USA
来源
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-PHARMACOLOGY TOXICOLOGY & ENDOCRINOLOGY | 1999年 / 123卷 / 02期
基金
澳大利亚研究理事会;
关键词
food intake; L-NAME; L-NMMA; marsupial; nitric oxide;
D O I
10.1016/S0742-8413(99)00022-5
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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 [r-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 r-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, r-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. (C) 1999 Elsevier Science Inc. All rights reserved.
引用
收藏
页码:145 / 151
页数:7
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