Food intake regulation in rodents: Y sub(5) or Y sub(1) NPY receptors or both?

• Published in: Canadian journal of physiology and pharmacology Vol. 78; no. 2; pp. 173 - 185
• Main Authors: Duhault, J, Boulanger, M, Chamorro, S, Boutin, JA, Della Zuana, O, Douillet, E, Fauchere, J-L, Feletou, M, Germain, M, Husson, B, Vega, A M, Renard, P, Tisserand, F
• Format: Journal Article
• Language: English
• Published: 01.02.2000
• ISSN: 0008-4212; 1205-7541

Neuropeptide Y (NPY), one of the most abundant peptides in rat and human brains, appears to act in the hypothalamus to stimulate feeding. It was first suggested that the NPY Y sub(1) receptor (Y sub(1)R) was involved in feeding stimulated by NPY. More recently a novel NPY receptor subtype (Y sub(5)R) was identified in rat and human as the NPY feeding receptor subtype. There is, however, no absolute consensus since selective Y sub(1)R antagonists also antagonize NPY-induced hyperphagia. Nevertheless, new anti-obesity drugs may emerge from further pharmacological characterization of the NPY receptors and their antagonists. A large panel of Y sub(1)R and Y sub(5)R antagonists (such as CGP71683A, BIBO3304, BIBP3226, 1229U91, and SYNAPTIC and BANYU derivatives but also patentable in-house-synthesized compounds) have been evaluated through in vitro and in vivo tests in an attempt to establish a predictive relationship between the binding selectivity for human receptors, the potency in isolated organs assays, and the inhibitory effect on food intake in both normal and obese hyperphagic rodents. Although these results do not allow one to conclude on the implication of a single receptor subtype at the molecular level, this approach is crucial for the design of novel NPY receptor antagonists with potential use as antiobesity drugs and for evaluation of their possible adverse peripheral side effects, such as hypotension.