Potentiation of histamine-induced catecholamine secretion by ouabain in cultured bovine adrenal chromaffin cells is dependent on calcium and sodium influx.
The effects of histamine on catecholamine secretion from cultured bovine adrenal chromaffin cells were studied in the presence of ouabain, an inhibitor of Na+-K+ ATPase. The purpose of this study was to determine whether Na+, as well as Ca2+, was involved in histamine receptor-mediated catecholamine secretion. Histamine (10(-8)-10(-5) M)-induced catecholamine secretion was markedly potentiated by addition of ouabain (10(-5) M) and was inhibited by a histamine-H1 receptor antagonist or incubation in a Ca2+-free medium. Histamine-induced 45Ca2+ influx was also potentiated by addition of ouabain. Ouabain alone or in the presence of histamine increased 22Na+ influx into the cells. In an additional set of experiments, cells were preincubated in the presence or absence of Na+ for 30 min (+/- histamine and ouabain), washed and then catecholamine secretion was measured following exposure to 2.2 mM Ca2+ for 15 min. Preincubation with histamine alone with or without Na+ had no effect of Ca2+-induced secretion of catecholamine. Preincubation with ouabain alone or with ouabain plus histamine produced a slight stimulation of catecholamine secretion in Na+-free medium and a large stimulation in Na+-containing medium. These results suggested that stimulation of the histamine-H1 receptor and inhibition of the Na+ pump both increase intracellular Na+ levels, resulting in increases in Ca2+ influx and catecholamine secretion.
Houchi
H
H
Department of Pharmacology, School of Medicine, The University of Tokushima, Kuramoto, Japan.
Yoshizumi
M
M
Minakuchi
K
K
Ishimura
Y
Y
Morita
K
K
Tamaki
T
T
Oka
M
M
D000313:Adrenal Medulla / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000187:drug effects* / Q000378:metabolism; D004357:Drug Synergism; D006632:Histamine / Q000494:pharmacology*; D017136:Ion Transport; D007700:Kinetics; D010042:Ouabain / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors
D002395:Catecholamines; D010042:Ouabain; D006632:Histamine; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D002118:Calcium