Cyclic GMP modulates depletion-activated Ca2+ entry in pancreatic acinar cells.
In the pancreatic acinar cell, hormonal stimulation causes a rise in the intracellular free Ca2+ concentration by activating the inositol 1,4,5-trisphosphate-mediated release of Ca2+ from intracellular stores (Berridge, M. J., and Irvine, R. F. (1989) Nature 341, 197-205). The released Ca2+ is, for the most part, extruded from the cell, necessitating a mechanism for Ca2+ entry and reloading of intracellular Ca2+ stores (Putney, J. W., Jr. (1990) Cell Calcium 11, 611-624; Rink, T. J. (1990) FEBS Lett. 268, 381-385). However, neither the mechanism of depletion-activated Ca2+ entry nor the signal that activates it is known. We report here that a sustained inward current of depletion-activated Ca2+ entry can be measured in pancreatic acinar cells using patch-clamp recording methods. Furthermore, the current can be blocked by an inhibitor of guanylyl cyclase, can be reactivated by 8-bromo-cGMP after inhibition, and can be activated in the absence of Ca2+ depletion by perfusing the cell with cGMP, but not cAMP. Intracellular perfusion with 1,3,4,5-inositol tetrakisphosphate did not activate an inward current, whereas perfusion with 2,4,5-inositol trisphosphate did activate an inward current. We conclude that cGMP may be an intracellular messenger that regulates depletion-activated Ca2+ entry.
Bahnson
T D
TD
Department of Medicine, University of California San Diego, School of Medicine, La Jolla 92093-0636.
Pandol
S J
SJ
Dionne
V E
VE
D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000187:drug effects / Q000502:physiology*; D000242:Cyclic AMP / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism* / Q000494:pharmacology*; D006162:Guanylate Cyclase / Q000494:pharmacology; D066298:In Vitro Techniques; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007295:Inositol Phosphates / Q000494:pharmacology; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects; D008954:Models, Biological; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015290:Second Messenger Systems / Q000187:drug effects / Q000502:physiology; D013997:Time Factors
D000634:Aminoquinolines; D015220:Calcium Channels; D007295:Inositol Phosphates; C081655:inositol-1,3,4,5-tetrakisphosphate; C016276:8-bromocyclic GMP; D015544:Inositol 1,4,5-Trisphosphate; C041715:6-anilino-5,8-quinolinedione; D000242:Cyclic AMP; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D002118:Calcium