Adrenomedullin and calcitonin gene-related peptide receptors in the rat adrenal cortex

The actions of calcitonin gene-related peptide (CGRP) and adrenomedullin on steroid hormone secretion from the rat zona glomerulosa are controversial, with reports in the literature of both stimulatory and inhibitory effects. It appears that these results previously obtained may depend on the nature of the receptors expressed by zona glomerulosa cells. The present study was designed to characterize CGRP and adrenomedullin binding in the rat adrenal zona glomerulosa. Specific binding for both peptides was observed, with two CGRP receptor sites found, and a single population of adrenomedullin receptors, but approximately twice the number of adrenomedullin binding sites. Messenger RNA analysis of the candidate genes for CGRP and adrenomedullin receptors revealed an abundance of both CRLR and RAMP1 mRNA, suggesting that these genes encode one of the CGRP receptors in this tissue. Much less RAMP2 expression was observed, however, which suggests that another gene product may account for adrenomedullin binding. There were very low levels of RAMP3 expression, but abundant L1 mRNA present, which may suggest that this rather controversial receptor has a role in the adrenal. The finding of distinct and specific adrenomedullin and CGRP binding in this tissue may account for the different effects these peptides appear to exert on adrenal function.