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-term 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.
Barth
Stephan W
SW
Federal Research Centre for Nutrition, Institute of Nutritional Physiology, Haid und Neu Str. 9, 76131 Karlsruhe, Germany. stephan.barth@bfe.uni-karlsruhe.de
Riediger
Thomas
T
Lutz
Thomas A
TA
Rechkemmer
Gerhard
G
D000682:Amyloid / Q000378:metabolism*; D000818:Animals; D018927:Anti-Asthmatic Agents / Q000494:pharmacology; D001522:Behavior, Animal; D002116:Calcitonin / Q000494:pharmacology; D004435:Eating / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D017403:In Situ Hybridization / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins; D058228:Islet Amyloid Polypeptide; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D058262:Receptor Activity-Modifying Protein 1; D058263:Receptor Activity-Modifying Protein 2; D058261:Receptor Activity-Modifying Proteins; D018003:Receptors, Calcitonin / Q000235:genetics / Q000378:metabolism*; D013356:Subfornical Organ / Q000378:metabolism*
D000682:Amyloid; D018927:Anti-Asthmatic Agents; D047908:Intracellular Signaling Peptides and Proteins; D058228:Islet Amyloid Polypeptide; D008565:Membrane Proteins; D016760:Proto-Oncogene Proteins c-fos; C545508:Ramp1 protein, rat; C545509:Ramp2 protein, rat; D058262:Receptor Activity-Modifying Protein 1; D058263:Receptor Activity-Modifying Protein 2; D058261:Receptor Activity-Modifying Proteins; D018003:Receptors, Calcitonin; C028815:salmon calcitonin; D002116:Calcitonin