Peripheral amylin activates circumventricular organs expressing calcitonin receptor a/b subtypes and receptor-activity modifying proteins in the rat

The pancreatic hormone amylin (AMY) and the AMY-receptor-agonist salmon-calcitonin (sCT) reduce short-tenn food-intake after binding to the area postrema (AP), a circumventricular organ (CVO) lacking blood-brain-barrier characteristics. AMY has also been proposed to induce drinking via another CVO, the subfornical organ (SFO). In cellular systems, AMY-binding is generated by interaction of calcitonin-receptor a/b (CT(a)/CT(b)) with receptor-activity modifying proteins (RAMPs). By using in situ hybridization, the codistribution of CT(a)/CT(b) with RAMP1-3 and c-fos was mapped in CVOs of rats. AMY and sCT induced c-fos within the SFO which contained CT(a) and/ or CT(b) and RAMP1/2 mRNA. AMY and sCT also activated AP neurons, which express the CT(a), but not the CT(b), receptor and RAMP2/3 mRNA. These data emphasize the important role of these structures as primary targets for circulating AMY. (C) 2003 Elsevier B.V. All rights reserved.