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

• Published in: The Journal of biological chemistry 1993-05, Vol.268 (15), p.10808-10812
• Main Authors: Bahnson, T.D., Pandol, S.J., Dionne, V.E.
• Format: Article
• Language: English
• Subjects: Aminoquinolines - pharmacology; Animals; Biological and medical sciences; Calcium - metabolism; Calcium Channels - drug effects; Calcium Channels - physiology; Cell physiology; Cyclic AMP - pharmacology; Cyclic GMP - analogs & derivatives; Cyclic GMP - metabolism; Cyclic GMP - pharmacology; Fundamental and applied biological sciences. Psychology; Guanylate Cyclase - pharmacology; In Vitro Techniques; Inositol 1,4,5-Trisphosphate - metabolism; Inositol Phosphates - pharmacology; Kinetics; Membrane and intracellular transports; Membrane Potentials - drug effects; Models, Biological; Molecular and cellular biology; Pancreas - cytology; Pancreas - drug effects; Pancreas - metabolism; Rats; Rats, Sprague-Dawley; Second Messenger Systems - drug effects; Second Messenger Systems - physiology; Time Factors
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1016/S0021-9258(18)82057-9

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.