Premium
Adrenomedullin Receptor Is Found Exclusively in Noradrenaline‐Secreting Cells of the Rat Adrenal Medulla
Author(s) -
Renshaw D.,
Thomson L. M.,
Michael G. J.,
Carroll M.,
Kapas S.,
Hinson J. P.
Publication year - 2000
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2000.0741766.x
Subject(s) - adrenomedullin , adrenal medulla , medicine , endocrinology , phenylethanolamine n methyltransferase , phenylethanolamine , receptor , adrenal gland , biology , calcitonin gene related peptide , calcitonin , chemistry , catecholamine , tyrosine hydroxylase , dopamine , neuropeptide
Adrenomedullin, originally identified in the adrenalmedulla, has binding sites in the adrenal gland; however, its role in theadrenal medulla is unclear. This study was designed to characteriseadrenomedullin binding sites in the rat adrenal medulla, using ligand bindingstudies, immunocytochemistry, and mRNA analysis. A single population ofspecific adrenomedullin receptors was identified in adrenal medullaryhomogenates. 125 I‐Adrenomedullin was displaced only byadrenomedullin 1‐50 and not by calcitonin gene‐related peptide oramylin at concentrations up to 100 nmol/L. The receptor K D was 3.64 nmol/L with a receptor density of 570 fmol/mg of protein. Analysis ofmRNA revealed that the genes encoding both the putative adrenomedullinreceptors, termed calcitonin receptor‐like receptor (CRLR) and L1, wereexpressed in the rat adrenal medulla. Dual‐colour indirect‐labelledimmunofluorescence was used to localise phenylethanolamine N ‐methyltransferase (PNMT) and the adrenomedullin receptor in the same section. PNMT is the enzyme that converts noradrenaline to adrenaline and is not expressed in noradrenaline‐secreting cells. These studies revealed that both CRLR and L1 were expressed only in cells that did not express PNMT, suggesting that adrenomedullin receptors are only found in noradrenaline‐secreting cells. Further evidence to support this conclusion was provided by the demonstration of colocalisation of adrenomedullin receptors with dopamine β‐hydroxylase, confirming the presence of the receptors in medullary chromaffin cells. Taken together, these data suggest that adrenomedullin acts through a specific adrenomedullin receptor in the rat adrenal medulla. RT‐PCR and northern blot analysis revealed greater abundance of mRNA for L1 than for CRLR, possibly suggesting that L1 may be the major adrenomedullin receptor expressed in this tissue. As it has been reported that adrenomedullin is synthesised predominantly by adrenaline‐secreting cells, it appears likely that adrenomedullin is a paracrine regulator in the adrenal medulla.