Ryanodine inhibits caffeine-evoked Ca2+ mobilization and catecholamine secretion from cultured bovine adrenal chromaffin cells.
The effects of ryanodine, a selective inhibitor of the Ca(2+)-induced Ca2+ release mechanism, on caffeine-evoked changes in cytosolic Ca2+ concentration ([Ca2+]i) and catecholamine secretion were investigated using cultured bovine adrenal chromaffin cells. Caffeine (5-40 mM) caused a concentration-dependent transient rise in [Ca2+]i and catecholamine secretion in Ca2+/Mg(2+)-free medium containing 0.2 mM EGTA. Ryanodine (5 x 10(-5) M) alone had no effect on either [Ca2+]i or catecholamine secretion. Although the application of ryanodine plus caffeine caused the same increase in both [Ca2+]i and catecholamine secretion as those induced by caffeine alone, ryanodine (4 x 10(-7) - 5 x 10(-5) M) irreversibly prevented the increase in both [Ca2+]i and catecholamine secretion resulting from subsequent caffeine application over a range of concentrations. The secretory response to caffeine was markedly enhanced by replacement of Na+ with sucrose in Ca2+/Mg(2+)-free medium, and this enhanced response was also blocked by ryanodine. Caffeine was found to decrease the susceptibility of the secretory apparatus to Ca2+ in digitonin-permeabilized cells. These results indicate that caffeine mobilizes Ca2+ from intracellular stores, the function of which is irreversibly blocked by ryanodine, resulting in the increase in catecholamine secretion in the bovine adrenal chromaffin cell.
Teraoka
H
H
Department of Pharmacology, Faculty of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Nakazato
Y
Y
Ohga
A
A
D000311:Adrenal Glands / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism*; D002417:Cattle; D002463:Cell Membrane Permeability / Q000187:drug effects; D002838:Chromaffin System / Q000166:cytology / Q000378:metabolism*; D004072:Digitonin / Q000494:pharmacology; D007425:Intracellular Membranes / Q000378:metabolism; D012433:Ryanodine / Q000494:pharmacology*; D012964:Sodium / Q000494:pharmacology
D002395:Catecholamines; D012433:Ryanodine; D002110:Caffeine; D012964:Sodium; D004072:Digitonin; D002118:Calcium