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Am J Physiol Regul Integr Comp Physiol 274: R1500-R1504, 1998;
0363-6119/98 $5.00
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Vol. 274, Issue 5, R1500-R1504, May 1998

RAPID COMMUNICATION
A potent neuropeptide Y antagonist, 1229U91, suppressed spontaneous food intake in Zucker fatty rats

A. Ishihara, T. Tanaka, A. Kanatani, T. Fukami, M. Ihara, and T. Fukuroda

Tsukuba Research Institute, Banyu Pharmaceutical Company, Okubo 3, Tsukuba 300-2611, Japan

Neuropeptide Y (NPY) is one of the most potent orexigenic substances known. 1229U91 was found to be a potent and selective NPY antagonist. To elucidate a physiological role of NPY in hyperphagia in obese animals, we studied the effect of 1229U91 on spontaneous food intake in obese and lean Zucker rats. The food intake of Zucker rats was suppressed by intracerebroventricular administration of 1229U91 more potently in obese than in lean animals without abnormal behavior (31.7 and 67.3% inhibition at doses of 10 and 30 µg, respectively, in Zucker fatty rats and 22.2% inhibition at 30 µg in lean rats). This compound markedly suppressed NPY-induced food intake at 30 µg but did not affect galanin-induced food intake, suggesting that the feeding suppression seen in Zucker fatty and lean rats is pharmacologically and behaviorally specific. These results suggest that NPY is involved in feeding behavior in Zucker fatty rats and that NPY contributes to feeding to a greater degree in Zucker fatty than in lean rats. The hyperphagia in Zucker fatty rats may be due to the abnormal overactivation of the NPYergic system.

feeding behavior; galanin; obesity


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