Mechanism of cholinergic stimulation of aldosterone secretion in bovine adrenal glomerulosa cells.
The effect of cholinergic stimulation on aldosterone secretion was examined in bovine adrenal glomerulosa cells. Both acetylcholine and carbachol stimulated aldosterone secretion in a dose-dependent manner. Acetylcholine-induced secretion was inhibited by atropine but not by hexamethonium, suggesting that cholinergic agonists act on muscarinic receptors. The mechanisms of cholinergic agonist action were compared with those of angiotensin II. Like angiotensin II, carbachol generated calcium signal in glomerulosa cells. When [3H]inositol-labeled cells were stimulated by carbachol, there was an immediate increase in [3H]inositol trisphosphate, followed by a relatively slow increase in [3H]inositol bisphosphate. Carbachol increased the cytosolic concentration of calcium transiently but not intracellular cAMP. Carbachol caused a rapid 3-fold increase in 45Ca fractional efflux ratio in 45Ca-prelabeled cells both in the presence and absence of extracellular calcium. Carbachol also increased calcium influx; however, carbachol-induced influx was smaller than that of angiotensin II. In a perifusion system, the time course of carbachol-induced aldosterone secretion was biphasic. However, when calcium influx was increased to a value similar to that in angiotensin II-treated cells by combination of carbachol and BAY K-8644, this combination induced a monophasic and sustained secretory pattern. These results indicate that muscarinic cholinergic agonists stimulate aldosterone secretion via the calcium messenger system, and the biphasic secretory response to cholinergic agonist is due to a smaller increase in calcium influx.
Kojima
I
I
Kojima
K
K
Shibata
H
H
Ogata
E
E
D000109:Acetylcholine / Q000494:pharmacology; D000302:Adrenal Cortex / Q000378:metabolism*; D000450:Aldosterone / Q000378:metabolism*; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D002217:Carbachol / Q000494:pharmacology; D002417:Cattle; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007295:Inositol Phosphates / Q000096:biosynthesis; D010277:Parasympathomimetics / Q000494:pharmacology*; D012636:Secretory Rate / Q000187:drug effects
D006584:Hexamethonium Compounds; D007295:Inositol Phosphates; D010277:Parasympathomimetics; D000804:Angiotensin II; D018738:Hexamethonium; D000450:Aldosterone; D001285:Atropine; D002217:Carbachol; D000242:Cyclic AMP; D000109:Acetylcholine; D002118:Calcium