Cyclic GMP modulates depletion-activated Ca2+ entry in pancreatic acinar cells

J Biol Chem. 1993 May 25;268(15):10808-12.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aminoquinolines / pharmacology
  • Animals
  • Calcium / metabolism*
  • Calcium Channels / drug effects
  • Calcium Channels / physiology*
  • Cyclic AMP / pharmacology
  • Cyclic GMP / analogs & derivatives
  • Cyclic GMP / metabolism*
  • Cyclic GMP / pharmacology*
  • Guanylate Cyclase / pharmacology
  • In Vitro Techniques
  • Inositol 1,4,5-Trisphosphate / metabolism
  • Inositol Phosphates / pharmacology
  • Kinetics
  • Membrane Potentials / drug effects
  • Models, Biological
  • Pancreas / cytology
  • Pancreas / drug effects
  • Pancreas / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Second Messenger Systems / drug effects
  • Second Messenger Systems / physiology
  • Time Factors


  • Aminoquinolines
  • Calcium Channels
  • Inositol Phosphates
  • inositol-1,3,4,5-tetrakisphosphate
  • 8-bromocyclic GMP
  • Inositol 1,4,5-Trisphosphate
  • 6-anilino-5,8-quinolinedione
  • Cyclic AMP
  • Guanylate Cyclase
  • Cyclic GMP
  • Calcium