BACKGROUND AND PURPOSE Amylin (Amy) is an important glucoregulatory peptide and AMY receptors are clinical targets for diabetes and obesity. Human (h) AMY receptor subtypes are complexes of the calcitonin (CT) receptor with receptor activity‐modifying proteins (RAMPs); their rodent counterparts have not been characterized. To allow identification of the most clinically relevant receptor subtype, the elucidation of rat (r) AMY receptor pharmacology is necessary.

EXPERIMENTAL APPROACH Receptors were transiently transfected into COS‐7 cells and cAMP responses measured in response to different agonists, with or without antagonists. Competition binding experiments were performed to determine rAmy affinity.

KEY RESULTS rCT was the most potent agonist of rCT_(a) receptors, whereas rAmy was most potent at rAMY_1(a) and rAMY_3(a) receptors. rAmy bound to these receptors with high affinity. Rat α‐calcitonin gene‐related peptide (CGRP) was equipotent to rAmy at both AMY receptors. Rat adrenomedullin (AM) and rAM2/intermedin activated all three receptors but were most effective at rAMY_3(a). AC187, AC413 and sCT_8‐32 were potent antagonists at all three receptors. rαCGRP_8‐37 displayed selectivity for rAMY receptors over rCT_(a) receptors. rAMY_8‐37 was a weak antagonist but was more effective at rAMY_1(a) than rAMY_3(a).

CONCLUSIONS AND IMPLICATIONS AMY receptors were generated by co‐expression of rCT_(a) with rRAMP1 or 3, forming rAMY_1(a) and rAMY_3(a) receptors, respectively. CGRP was more potent at rAMY than at hAMY receptors. No antagonist tested was able to differentiate the rAMY receptor subtypes. The data emphasize the need for and provide a useful resource for developing new CT or AMY receptor ligands as pharmacological tools or potential clinical candidates.

LINKED ARTICLES This article is part of a themed section on Secretin Family (Class B) G Protein‐Coupled Receptors. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2012.166.issue‐1