Effects of caffeine on cholinergic agonist- and K(+)-induced cytosolic Ca++ signals and secretion in porcine adrenal chromaffin cells

Y Xu and EJ Forsberg

Department of Physiology, University of Wisconsin, Madison.

A possible involvement of Ca(++)-induced Ca++ release mechanisms in muscarinic agonist-induced, extracellular Ca(++)-independent, catecholamine secretion in porcine adrenal chromaffin cells was examined. Caffeine was found to induce rapid increases in cytosolic Ca++ ([Ca++]in) in a ryanodine-sensitive manner. In addition, caffeine pretreatment inhibited methacholine (a selective muscarinic agonist)- and thapsigargin (thapsigargin depletes inositol 1,4,5-trisphosphate- sensitive Ca++ pools)-induced increases in [Ca++]in as well as methacholine-induced secretion. However, several lines of evidence suggest that Ca(++)-induced Ca++ release does not play a major role in methacholine-induced increases in [Ca++]in. Instead, the results are more compatible with the notion that Ins(1,4,5)P3 and caffeine activate Ca++ release from the same intracellular Ca++ pool, or that distinct Ca++ pools, if they exist, can equilibrate rapidly. Caffeine pretreatment was also observed to eliminate nicotinic responses but not elevated extracellular K(+)-induced responses, suggesting that caffeine blocks nicotinic receptor-channels.

Volume 264, Issue 2, pp. 770-775, 02/01/1993
Copyright © 1993 by American Society for Pharmacology and Experimental Therapeutics