Excitation-secretion coupling: involvement of potassium channels in ACTH-stimulated rat adrenocortical cells.
The mechanism by which ACTH stimulates calcium influx and steroid secretion was studied using rat adrenal glomerulosa cells, which were either freshly isolated or maintained in primary culture for 3 days. The potassium channel blocker tetraethylammonium chloride (TEA) stimulated twofold both corticosterone and aldosterone secretion; this stimulation was lower than that induced by ACTH at low concentrations (10 pmol/l). However, TEA and ACTH induced similar increases in Ca2+ influx and inositol phosphate accumulation. The three responses (steroid secretion, calcium influx and inositol phosphate accumulation) induced by TEA or low concentrations of ACTH were blocked by CoCl2. The greater stimulatory effect on steroid secretion of 10 nmol ACTH/l was decreased but not blocked by CoCl2. These data further document the complex mechanism of action of ACTH. It is postulated that, at low concentrations, ACTH binds preferentially to the high-affinity site of its receptor, leading to calcium influx by depolarization of the membrane potential, and to steroid secretion predominantly through an inositol phosphate- and Ca2+-stimulated pathway and also a cyclic AMP pathway. At higher concentrations, the hormone also binds to the low-affinity site of its receptor, largely stimulating cyclic AMP production and further increasing steroid secretion.
Gallo-Payet
N
N
Department of Medicine, Faculty of Medicine, University of Sherbrooke, Quebec, Canada.
Payet
M D
MD
D000324:Adrenocorticotropic Hormone / Q000494:pharmacology*; D000450:Aldosterone / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D003345:Corticosterone / Q000378:metabolism; D000242:Cyclic AMP / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D005260:Female; D007295:Inositol Phosphates / Q000096:biosynthesis; D015221:Potassium Channels / Q000378:metabolism*; D011282:Pregnenediones / Q000378:metabolism*; D051381:Rats; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D015384:Zona Glomerulosa / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism
D007295:Inositol Phosphates; D015221:Potassium Channels; D011282:Pregnenediones; D013757:Tetraethylammonium Compounds; D000450:Aldosterone; D019789:Tetraethylammonium; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D002118:Calcium; D003345:Corticosterone