Local production and action of adrenomedullin in the rat adrenal zona glomerulosa.
This study was designed to investigate the synthesis and action of adrenomedullin in the rat adrenal gland. The results obtained from in situ hybridization and immunocytochemical studies suggest that adrenomedullin is synthesized not only in the medulla, but also within the zona glomerulosa of the rat adrenal cortex. Findings from in situ hybridization and binding studies also suggested that specific adrenomedullin receptors are expressed in the zona glomerulosa, and that low levels are present in the inner zones of the cortex. The Kd of the zona glomerulosa adrenomedullin receptor (5.5 nmol/l) suggests that it may respond to locally produced adrenomedullin rather than circulating concentrations of the peptide, which are in a lower range. It was found that adrenomedullin acted on zona glomerulosa cells in vitro to stimulate aldosterone release and cAMP formation, but in this tissue did not stimulate inositol phosphate turnover. The effect of adrenomedullin on aldosterone secretion was significantly attenuated by a protein kinase A inhibitor, suggesting that cAMP mediates the effects of adrenomedullin on aldosterone secretion. Adrenomedullin did not significantly affect the response of zona glomerulosa cells to stimulation by either ACTH or angiotensin II. Adrenomedullin did not affect the release of catecholamines, either adrenaline or noradrenaline, by intact adrenal capsular tissue. These data suggest that both adrenomedullin and its specific receptor are expressed in the rat adrenal zona glomerulosa, leading to the hypothesis that adrenomedullin may have an autocrine/paracrine role in the regulation of the rat adrenal zona glomerulosa.
Kapas
S
S
Department of Oral Pathology, St Bartholomew's, London, UK.
Martínez
A
A
Cuttitta
F
F
Hinson
J P
JP
D053607:Adrenomedullin; D000450:Aldosterone / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004837:Epinephrine / Q000378:metabolism; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007546:Isoquinolines / Q000494:pharmacology; D008565:Membrane Proteins / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010455:Peptides / Q000378:metabolism* / Q000494:pharmacology; D011485:Protein Binding; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D058265:Receptors, Adrenomedullin; D018000:Receptors, Peptide; D013449:Sulfonamides; D015384:Zona Glomerulosa / Q000187:drug effects / Q000378:metabolism*
D004791:Enzyme Inhibitors; D007546:Isoquinolines; D008565:Membrane Proteins; D010455:Peptides; D058265:Receptors, Adrenomedullin; D018000:Receptors, Peptide; D013449:Sulfonamides; D000804:Angiotensin II; D053607:Adrenomedullin; D000450:Aldosterone; D015544:Inositol 1,4,5-Trisphosphate; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D017868:Cyclic AMP-Dependent Protein Kinases; D009638:Norepinephrine; D004837:Epinephrine