Role of thapsigargin-sensitive intracellular Ca2+ pools in secretion induced by muscarinic agonists in porcine adrenal chromaffin cells.
The role of inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]-sensitive Ca2+ pools in secretion, induced by muscarinic agonists in porcine adrenal chromaffin cells, was studied. Activation of muscarinic receptors, as in other species, was found to increase inositol phosphate production including that of Ins(1,4,5)P3. Treatment of cells with thapsigargin, which is known to deplete Ins(1,4,5)P3-sensitive Ca2+ pools, eliminated the initial transient component of increases in the cytosolic free Ca2+ concentration ([Ca2+]in) induced by the muscarinic agonist, methacholine, in both the presence and the absence of extracellular Ca2+. Thapsigargin treatment also decreased methacholine-induced secretion by about 30% in the presence of extracellular Ca2+ and essentially eliminated secretion that occurred independently of extracellular Ca2+ (which was about 30% of the secretory response that occurred in the presence of extracellular Ca2+). Thapsigargin itself had no effect on inositol phosphate production. These results indicate that about 30% of muscarinic agonist-induced secretion is mediated by the release of Ca2+ from Ins(1,4,5)P3- and thapsigargin-sensitive intracellular Ca2+ pools. These results also suggest that Ca2+ influx activated by muscarinic agonists is not due to depletion of intracellular Ca2+ pools, as prior depletion of these pools had no effect on the portion of the methacholine-induced secretory response and [Ca2+]in signal that was dependent on extracellular Ca2+.
Xu
Y
Y
Department of Physiology, University of Wisconsin, Madison 53706.
Duarte
E P
EP
Forsberg
E J
EJ
D000818:Animals; D002118:Calcium / Q000032:analysis* / Q000378:metabolism / Q000502:physiology*; D000252:Calcium-Transporting ATPases / Q000037:antagonists & inhibitors*; D002395:Catecholamines / Q000378:metabolism*; D002478:Cells, Cultured; D002838:Chromaffin System / Q000166:cytology* / Q000378:metabolism* / Q000648:ultrastructure; D005109:Extracellular Matrix / Q000737:chemistry*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D016210:Methacholine Chloride / Q000494:pharmacology; D010277:Parasympathomimetics / Q000494:pharmacology*; D011976:Receptors, Muscarinic / Q000032:analysis / Q000187:drug effects / Q000502:physiology; D013552:Swine; D013729:Terpenes / Q000494:pharmacology*; D019284:Thapsigargin
D002395:Catecholamines; D007295:Inositol Phosphates; D010277:Parasympathomimetics; D011976:Receptors, Muscarinic; D013729:Terpenes; D016210:Methacholine Chloride; D019284:Thapsigargin; D015544:Inositol 1,4,5-Trisphosphate; D000252:Calcium-Transporting ATPases; D002118:Calcium