Calcitonin-induced anorexia in rats: A structure-activity study by intraventricular injections.

Abstract

The anorectic potency of salmon, porcine and human calcitonins (sCT, pCT and hCT, respectively) and two sCT-fragments were compared in rats. Intraventricular injections of sCT (0.062 and 0.031 nmole/animal) significantly reduced the normal feeding and body weight. The effect appeared to be dose-dependent, reversible and lasted longer than 6 hr. No anorexia ensued, however, on injections of mammalian hormones though tested in relatively high doses (pCT: up to 3.7 nmole, hCT: 3.7 nmole). The C-terminal fragments of sCT, sCT (10-32) and sCT (22-32) were also found to be devoid of anorectic activity; but when administered with sCT, the longer fragment (1.2 nmole) significantly decreased the effect of sCT and even the shorter one (18 nmole) tended to act as an antagonist. This property was not recorded with pCT and hCT in the doses examined. On the one hand, these results indicate a novel specificity of the anorectic receptor in rat brain; and on the other hand, they seem to strongly argue against the hypothesis that in mammals thyroidal calcitonin secreted postprandially might participate in the regulation of subsequent feeding, unless the presence of the sCT-like molecule can be detected in mammals. All the more because detection of such a molecule must await development of a specific assay, the antagonistic property of the sCT fragment found herein would have use for clarifying the physiological significance of the anorectic receptor which is possibly in the hypothalamus.