Cyclic GMP regulates free cytosolic calcium in the pancreatic acinar cell.
The present studies were performed in order to measure the effects of cyclic GMP (cGMP) on the regulation of free cytosolic calcium [( Ca2+]i) in the pancreatic acinar cell. In guinea pig dispersed pancreatic acini the findings demonstrated that the Ca2+ ionophore, Br A23187, caused a sustained increase in [Ca2+]i in the presence of 3 mM CaCl2 in the media and a transient 20 fold rise in cellular cGMP followed by a sustained 3-4 fold rise in cellular cGMP. Increasing cellular cGMP with nitroprusside, hydroxylamine or dibutyryl cGMP had no effect on resting [Ca2+]i. However, these agents attenuated the increase in [Ca2+]i resulting from Br A23187-induced Ca2+ influx. Nitroprusside also attenuated the carbachol-induced sustained rise in [Ca2+]i that resulted from Ca2+ influx. The nitroprusside effect on carbachol-stimulated acini occurred without decreasing Ca2+ influx across the plasma membrane or alteration in the mobilization of Ca2+ from the intracellular agonist-sensitive pool. Inhibition of the increase in cellular cGMP caused by Br A23187 by the guanylate cyclase inhibitor, 6-anilino-5,8-quinolinedione (LY83583), resulted in augmentation of the increase in [Ca2+]i. This augmentation was reversed with dibutyryl cGMP. These results indicated that cGMP regulated [Ca2+]i in the pancreatic acinar cell. The mechanism involves the removal of Ca2+ from the cytoplasm.
Pandol
S J
SJ
Department of Medicine, Veterans Administration, San Diego, California.
Schoeffield-Payne
M S
MS
D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000032:analysis / Q000378:metabolism*; D006152:Cyclic GMP / Q000502:physiology*; D003600:Cytosol / Q000737:chemistry / Q000378:metabolism*; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000378:metabolism; D006168:Guinea Pigs; D006898:Hydroxylamines / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D010179:Pancreas / Q000166:cytology* / Q000378:metabolism; D013189:SRS-A / Q000037:antagonists & inhibitors
D000634:Aminoquinolines; D006898:Hydroxylamines; D013189:SRS-A; D009599:Nitroprusside; D003995:Dibutyryl Cyclic GMP; D000001:Calcimycin; C041715:6-anilino-5,8-quinolinedione; D006162:Guanylate Cyclase; D006152:Cyclic GMP; D002118:Calcium