Correlation between secretagogue-induced Ca2+ influx, intracellular Ca2+ levels and secretion of catecholamines in cultured adrenal chromaffin cells.
Catecholamine secretion induced by various secretagogues in cultured bovine chromaffin cells has been correlated with Ca2+ influx and intracellular Ca2+ concentrations. Nicotine and high K+ caused prompt secretion of catecholamines from cells. Coincidently, both secretagogues evoked 45[Ca2+] influx with a parallel increase in free intracellular Ca2+ concentration, as determined by Quin 2 fluorescence. However, the rate of return of Ca2+ level to baseline after nicotine stimulation was more rapid than after K+ stimulation. In comparison, stimulation with veratridine produced a slow and prolonged Ca2+ influx accompanied by lower levels of intracellular Ca2+ than those observed after nicotine or K+ stimulation. Yet, during 15 min of stimulation, veratridine induced a substantial catecholamine release, which was larger than that obtained after nicotine or K+ stimulations. The Ca2+ ionophore A23187 (1 microM) induced a pronounced increase in intracellular Ca2+ levels, but did not evoke any significant catecholamine release. Finally, addition of the Ca2+ channel blocker verapamil following stimulation, at a time when intracellular Ca2+ concentration was at its peak level, did not affect the rate of decline in intracellular free Ca2+ concentration but promptly blocked Ca2+ uptake and catecholamine secretion. These findings suggest that the rate of Ca2+ influx, rather than the absolute level of intracellular Ca2+ concentration, determines the rate and extent of catecholamine release.
Heldman
E
E
Israel Institute for Biological Research, Ness Ziona, Israel.
Barg
J
J
Vogel
Z
Z
Pollard
H B
HB
Zimlichman
R
R
D000634:Aminoquinolines; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism* / Q000502:physiology; D002132:Calcium Radioisotopes; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D018679:Cholinergic Agonists / Q000494:pharmacology; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism*; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology; D005456:Fluorescent Dyes; D007476:Ionophores / Q000494:pharmacology; D007700:Kinetics; D009538:Nicotine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D013268:Stimulation, Chemical; D014701:Veratridine / Q000494:pharmacology
D000634:Aminoquinolines; D002132:Calcium Radioisotopes; D002395:Catecholamines; D018679:Cholinergic Agonists; D005456:Fluorescent Dyes; D007476:Ionophores; D000001:Calcimycin; D009538:Nicotine; D014701:Veratridine; C035739:Quin2; D011188:Potassium; D002118:Calcium