NEUROPEPTIDE-Y AND THE DEVELOPMENT OF CANCER ANOREXIA

Objective The authors determined whether radioligand binding of neurop eptide Y (NPY) to hypothalamus taken from nonanorectic and anorectic t umor-bearing rats was altered as compared with similar tissue taken fr om freely-feeding and food-restricted control rats. Summary Background Data Previous results indicate that tumor-bearing rats exhibit a refr actory feeding response to NPY, the most potent feeding stimulus known . Additional studies indicate that the concentration of NPY in the hyp othalamus of anorectic tumor-bearing rats is decreased as compared wit h freely-feeding or food-restricted control rats. Methods Because thes e observations of decreased response to exogenous peptide in the prese nce of decreased endogenous levels suggest an alteration in hypothalam ic NPY receptors, this study investigated binding of I-125-NPY to hypo thalamic membranes of tumor-bearing and control rats. Results Determin ations of receptor affinity for NPY (half maximal concentration for di splacement) indicated a 20-fold decrease in affinity with the developm ent of anorexia, which changed to an 80-fold decrease during severe an orexia. Receptor density, as indicated by specific binding, exhibited only a 30% decrease, even during severe anorexia. Conclusions These re sults suggest major alterations in NPY receptor mechanisms in experime ntal cancer anorexia, with receptor affinity being decreased progressi vely as the rats become more anorectic. The absence of a compensatory up-regulation in receptor density in the presence of decreased endogen ous NPY concentrations indicate dysfunction in receptor regulatory mec hanisms. This receptor aberration may be the central nervous system ba sis for the etiology of cancer anorexia.