Fluoroaluminate activation of different components of the calcium signal in an exocrine cell.
In isolated cells from the avian supra-orbital nasal gland, used as a model for exocrine ion secretion, addition of NaF (2-15 mM) produced a slow Al3(+)-enhanced increase in intracellular Ca2+ concn. ([Ca2+]i), resulting in a more than 2-fold sustained elevation in [Ca2+]i. Simultaneously, cellular Ins(1,4,5)P3 contents became markedly elevated, suggesting an AlF4- activation of a phospholipase C-specific G-protein. Subsequent addition of the muscarinic agonist carbachol failed to produce any further sustained increase in [Ca2+]i, indicating that the AlF4(-)-induced increase in [Ca2+]i involves a Ca2(+)-entry pathway identical with that activated by carbachol. In low-Ca2+ media (extracellular [Ca2+] = 0.04 mM) no such increase in [Ca2+]i, either sustained or transient, is seen, although cellular Ins(1,4,5)P3 levels were markedly elevated. Despite the failure to observe any change in [Ca2+]i in the low-Ca2+ medium, estimation of the size of the agonist-sensitive Ca2+ stores (determined as the magnitude of the transient change in [Ca2+]i induced by carbachol) revealed that these are progressively emptied by the action of AlF4-. However, the onset of this emptying showed an initial lag period of at least 2 min (with 5 mM-NaF plus 10 microM-AlCl3). In marked contrast, determinations of the magnitude of the Ca2(+)-entry pathway under identical conditions showed that this was significantly activated after as little as 1 min of AlF4- treatment. This suggests that, under these conditions, activation of Ca2+ entry in these cells preceded the release of Ca2+ from agonist-sensitive stores, contradicting current models in which the receptor-enhanced entry of extracellular Ca2+ is entirely dependent on, and subsequent to, the prior release of Ca2+ from the intracellular stores.
Shuttleworth
T J
TJ
Department of Physiology, University of Rochester School of Medicine and Dentistry, NY 14642.
D000535:Aluminum / Q000494:pharmacology*; D000077410:Aluminum Chloride; D017607:Aluminum Compounds; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism / Q000494:pharmacology*; D004372:Ducks; D005088:Exocrine Glands / Q000187:drug effects / Q000378:metabolism*; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007700:Kinetics; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects*; D012969:Sodium Fluoride / Q000494:pharmacology*
D017607:Aluminum Compounds; D002712:Chlorides; D011976:Receptors, Muscarinic; D000077410:Aluminum Chloride; D001285:Atropine; D015544:Inositol 1,4,5-Trisphosphate; D002217:Carbachol; D012969:Sodium Fluoride; D000535:Aluminum; D002118:Calcium