title: Cyclic GMP mediates the agonist-stimulated increase in plasma membrane calcium entry in the pancreatic acinar cell.
abstract: 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.
authors.affiliation: Department of Medicine, Veterans Administration, San Diego, California.
authors.forename: S J
authors.initials: SJ
authors.lastname: Pandol
authors.forename: M S
authors.initials: MS
authors.lastname: Schoeffield-Payne
mesh_terms: 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
chemical_list: 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