Attenuation of the anorectic effects of cholecystokinin and bombesin by the specific amylin antagonist AC 253

Previous studies provided evidence for an interaction between the satiety e ffects of cholecystokinin (CCK), bombesin (BBS), and amylin. Amylin release d in response to CCK (or BBS) was supposed to mediate part of CCK's (or BBS 's) anorectic effect since the amylin and calcitonin gene-related peptide ( CGRP) antagonist CGRP 8-37 attenuated their anorectic action. Due to the lo w specificity of CGRP 8-37 for amylin vs. CGRP binding sites, the aim of th e present study was to test whether the specific amylin antagonist AC 253 a lso influenced the anorectic effects of CCK and BBS. Injections took place at dark onset in 24-h food-deprived rats. At a dose that attenuated the ano rectic effect of amylin (5 mug/kg), the amylin antagonist AC 253 (500 mug/k g) significantly attenuated the anorectic effects of CCK and BBS (0.5 mug/k g). It can therefore be concluded that amylin, rather than CGRP, mediates p art of the anorectic effects of CCK and BBS. (C) 2000 Elsevier Science Inc. All rights reserved.