EFFECTS OF CAFFEINE ON CHOLINERGIC AGONIST-INDUCED AND K+-INDUCED CYTOSOLIC CA++ SIGNALS AND SECRETION IN PORCINE ADRENAL CHROMAFFIN CELLS

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.