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 effects of cholecystokinin (CCK), bombesin (BBS), and amylin. Amylin released 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 low specificity of CGRP 8-37 for amylin vs. CGRP binding sites, the aim of the present study was to test whether the specific amylin antagonist AC 253 also 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 anorectic effect of amylin (5 microg/kg), the amylin antagonist AC 253 (500 microg/kg) significantly attenuated the anorectic effects of CCK and BBS (0.5 microg/kg). It can therefore be concluded that amylin, rather than CGRP, mediates part of the anorectic effects of CCK and BBS.