Inhibition of Na+-pump enhances carbachol-induced influx of 45Ca2+ and secretion of catecholamines by elevation of cellular accumulation of 22Na+ in cultured bovine adrenal medullary cells.
In bovine adrenal medullary cells, we reported that 22Na+ influx via nicotinic receptor-associated Na+ channels is involved in 45Ca2+ influx, a requisite for initiating the secretion of catecholamines (Wada et al. 1984, 1985 b). In the present study, we investigated whether the inhibition of Na+-pump modulates carbachol-induced 22Na+ influx, 45Ca2+ influx and catecholamine secretion in cultured bovine adrenal medullary cells. We also measured 86Rb+ uptake by the cells to estimate the activity of Na+,K+-ATPase. Ouabain and extracellular K+ deprivation remarkably potentiated carbachol-induced 22Na+ influx, 45Ca2+ influx and catecholamine secretion; this potentiation of carbachol-induced 45Ca2+ influx and catecholamine secretion was not observed in Na+ free medium. Carbachol increased the uptake of 86Rb+; this increase was inhibited by hexamethonium and d-tubocurarine. In Na+ free medium, carbachol failed to increase 86Rb+ uptake. Ouabain inhibited carbachol-induced 86Rb+ uptake in a concentration-dependent manner, as it increased the accumulation of cellular 22Na+. These results suggest that Na+ influx via nicotinic receptor-associated Na+ channels increases the activity of Na+,K+-ATPase and the inhibition of Na+,K+-ATPase augmented carbachol-induced Ca2+ influx and catecholamine secretion by potentiating cellular accumulation of Na+. It seems that nicotinic receptor-associated Na+ channels and Na+,K+-ATPase, both modulate the influx of Ca2+ and secretion of catecholamines by accommodating cellular concentration of Na+.
D000313:Adrenal Medulla / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000037:antagonists & inhibitors / Q000494:pharmacology; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism*; D009116:Muscarine / Q000378:metabolism; D009538:Nicotine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D011188:Potassium / Q000502:physiology; D011868:Radioisotopes; D012413:Rubidium; D012964:Sodium / Q000378:metabolism*
D002395:Catecholamines; D007473:Ion Channels; D011868:Radioisotopes; D010042:Ouabain; D009538:Nicotine; D009116:Muscarine; D002217:Carbachol; D012964:Sodium; D012413:Rubidium; D011188:Potassium; D002118:Calcium