Ryanodine Inhibits Caffeine‐Evoked Ca2+ Mobilization and Catecholamine Secretion from Cultured Bovine Adrenal Chromaffin Cells

Publisher Website
Google Scholar
Abstract
The effects of ryanodine, a selective inhibitor of the Ca2+‐induced Ca2+ release mechanism, on caffeine‐evoked changes in cytosolic Ca2+ concentration ([Ca2+]i) and cate‐cholamine 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+/Mg2+‐free medium containing 0.2 mM EGTA. Ryanodine (5 × 10–5M) 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 × 10–7–5 × 10–5M) 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/Mg2+‐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.