Potentiation by ouabain of bradykinin-induced catecholamine secretion and calcium influx into cultured bovine adrenal chromaffin cells: evidence for involvement of Na+ influx associated with the bradykinin B2-receptor.
The effect of bradykinin (BK), in the presence of ouabain, an inhibitor of Na(+)-K+ ATPase, on catecholamine (CA) secretion was studied in cultured bovine adrenal chromaffin cells, to determine whether Na+, as well as Ca2+, is involved in BK-receptor mediated CA secretion. BK (10(-8)-10(-5) M)-induced CA secretion was markedly potentiated by addition of ouabain (10(-5) M), was blocked by a BK-B2 receptor antagonist, and was decreased in Ca(2+)-free medium. BK-induced increase in 45Ca2+ influx was also potentiated by addition of ouabain. The cultured cells were first incubated with BK for 30 min in Ca(2+)-free medium in the presence or absence of ouabain and then stimulated for 15 min with Ca(2+)-medium without BK or ouabain. Prior stimulation of the cells, BK induced 22Na+ influx and increased Ca(2+)-induced CA secretion and these stimulatory effects of BK were potentiated by added ouabain. When the cells were stimulated with BK and ouabain in Na(+)-free sucrose medium, the Ca(2+)-induced CA secretion was greatly reduced. These results indicated that activation of the BK-B2 receptor and inhibition of the Na+ pump both increase the intracellular Na+ level, resulting in increase in Ca2+ influx and CA secretion.
Murakumo
Y
Y
Department of Pharmacology, School of Medicine, University of Tokushima, Japan.
Houchi
H
H
Minakuchi
K
K
Yoshizumi
M
M
Oka
M
M
D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002478:Cells, Cultured; D002838:Chromaffin System / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D010042:Ouabain / Q000494:pharmacology*; D018002:Receptors, Bradykinin / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects; D013997:Time Factors
D002395:Catecholamines; D018002:Receptors, Bradykinin; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D001920:Bradykinin; D002118:Calcium