Amylin receptors mediate the anorectic action of salmon calcitonin (sCT)

The teleost salmon calcitonin (sCT), but not mammalian CT, shows similar bi ologic actions in the skeletal muscle as amylin and calcitonin gene-related peptide (CGRP). The peptides have also been shown to reduce food intake in rats. Because sCT, but not amylin, binds irreversibly to amylin binding si tes, the aim of the present study was to compare the anorectic potency of b oth peptides. To determine whether sCT reduces food intake through interact ion with amylin binding sites, we also tested whether appropriate antagonis ts (CGRP 8-37, AC 187) attenuate the anorectic effect of sCT. Finally, we w anted to know whether rat calcitonin (rCT) and sCT reduce food intake to th e same extent. Peptides were injected intraperitoneally at dark onset in 24 h food-deprived rats. At doses of 5 or 0.5 mu g/kg, the anorectic effect o f sCT was more potent and lasted much longer (e.g. 5 mu g/kg: sCT > 10 h; a mylin approx. 2 h) than that of amylin. Both CGRP 8-37 and AC 187 (10 mu g/ kg) markedly reduced the anorectic action of sCT (0.5 mu g/kg). In contrast to sCT, rCT (0.5 mu g/kg) had no effect on food intake. It is concluded th at sCT's anorectic effect is partly mediated by amylin receptors. Irreversi ble binding of sCT to amylin receptors may lead ro a stronger and prolonged effect in comparison to amylin due to a sustained activation of the bindin g sites. Similar to other actions of CTs, the anorectic potency of sCT in r ats was higher than that of mammalian (rat) CT. This agrees with binding pr ofiles of amylin, sCT, and rCT at amylin binding sites as observed in in vi tro studies. (C) 2000 Elsevier Science Inc. All rights reserved.