Effects of caffeine on cholinergic agonist- 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.
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Department of Physiology, University of Wisconsin, Madison.
Forsberg
E J
EJ
D000818:Animals; D002110:Caffeine / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002395:Catecholamines / Q000378:metabolism; D002478:Cells, Cultured; D002837:Chromaffin Granules / Q000187:drug effects / Q000378:metabolism*; D003600:Cytosol / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D015544:Inositol 1,4,5-Trisphosphate / Q000494:pharmacology; D016210:Methacholine Chloride / Q000494:pharmacology; D009538:Nicotine / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology*; D011978:Receptors, Nicotinic / Q000187:drug effects; D012433:Ryanodine / Q000494:pharmacology; D013552:Swine; D013729:Terpenes / Q000494:pharmacology; D019284:Thapsigargin
D002395:Catecholamines; D010277:Parasympathomimetics; D011978:Receptors, Nicotinic; D013729:Terpenes; D016210:Methacholine Chloride; D012433:Ryanodine; D002110:Caffeine; D019284:Thapsigargin; D009538:Nicotine; D015544:Inositol 1,4,5-Trisphosphate; D011188:Potassium; D002118:Calcium