Cyclic GMP mediates the agonist-stimulated increase in plasma membrane calcium entry in the pancreatic acinar cell.
The present studies were performed to determine the role of cyclic GMP in regulating agonist mediated calcium entry in the pancreatic acinar cell. In guinea pig-dispersed pancreatic acini the findings demonstrated that carbachol stimulated a transient 20-40-fold rise in cellular cyclic GMP followed by a sustained 3-4-fold rise in cellular cyclic GMP. The guanylate cyclase inhibitor, 6-anilino-5,8-quinolinedione (LY83583), caused a dose-dependent inhibition of carbachol-stimulated increases in cellular cyclic GMP both during the initial transient large increase in cyclic GMP and the sustained increase in cyclic GMP. LY83583 also inhibited cellular Ca2+ influx during carbachol stimulation and reloading of the agonist-sensitive pool of Ca2+ at the termination of carbachol stimulation with atropine. The effect of the inhibition on reloading of the agonist-sensitive pool was secondary to its effects on the plasma membrane C2+ entry. The addition of dibutyryl cyclic GMP to LY83583-treated acini restored Ca2+ influx across the plasma membrane. Nitroprusside increased both cellular cyclic GMP and the rate of Ca2+ influx. During periods when plasma membrane Ca2+ entry was activated, cellular cyclic GMP levels were increased. These results suggest that agonist-induced increases in cellular cyclic GMP are necessary and sufficient to mediate the effects of the agonist on the plasma membrane Ca2+ entry mechanism.
Pandol
S J
SJ
Department of Medicine, Veterans Administration, San Diego, California.
Schoeffield-Payne
M S
MS
D000634:Aminoquinolines / Q000494:pharmacology*; D000818:Animals; D001572:Benzofurans; D002118:Calcium / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D005456:Fluorescent Dyes; D016257:Fura-2; D006168:Guinea Pigs; D066298:In Vitro Techniques; D007700:Kinetics; D009599:Nitroprusside / Q000494:pharmacology; D010179:Pancreas / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D013189:SRS-A / Q000037:antagonists & inhibitors
D000634:Aminoquinolines; D001572:Benzofurans; D005456:Fluorescent Dyes; D013189:SRS-A; D009599:Nitroprusside; D002217:Carbachol; C041715:6-anilino-5,8-quinolinedione; D006152:Cyclic GMP; D002118:Calcium; D016257:Fura-2