Inhibition by amiloride of ouabain-evoked catecholamine secretion from cultured adrenal chromaffin cells: evidence for its blocking action on interaction between ouabain and Na+/K(+)-pump.
The effect of amiloride on ouabain-evoked catecholamine secretion was investigated in primary cultures of bovine adrenal chromaffin cells. Catecholamine secretion evoked by ouabain was inhibited markedly by amiloride, but the secretion evoked by Na+ removal was not affected by the drug. In contrast, adriamycin, a putative inhibitor of the Na(+)-Ca++ exchange, inhibited the secretion evoked by Na+ removal as well as that evoked by ouabain. The inhibitory action of amiloride on the ouabain-evoked secretion was therefore considered to be due to its action on other mechanism(s) than the Na(+)-Ca++ exchange process. Further studies showed that the uptake of 86Rb+ into the cells was slightly but significantly reduced by amiloride, and the inhibitory action of ouabain on 86Rb+ uptake was considerably blocked by this drug under the experimental conditions in which the inhibition of ouabain-evoked secretion was observed. The binding of [3H] ouabain to the intact cells was also inhibited by amiloride under the same conditions. These results suggest that amiloride may inhibit ouabain-evoked catecholamine secretion as a consequence of blocking the inhibitory action of ouabain on the plasma membrane Na+/K(+)-pump in adrenal chromaffin cells.
Morita
K
K
Department of Pharmacology, Tokushima University School of Medicine, Japan.
Azuma
M
M
Hamano
S
S
Oka
M
M
Teraoka
K
K
D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism; D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002462:Cell Membrane / Q000187:drug effects; D002478:Cells, Cultured; D002838:Chromaffin System / Q000187:drug effects* / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D010042:Ouabain / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D012413:Rubidium / Q000493:pharmacokinetics; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects*
D002395:Catecholamines; D010042:Ouabain; D000584:Amiloride; D004317:Doxorubicin; D000254:Sodium-Potassium-Exchanging ATPase; D012413:Rubidium