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Signal transduction; Indomethacin; Protein kinase A inhibitor
Abstract:
In this study we have examined the effects of prostaglandin E2 (PGE2), the cyclooxygenase inhibitor, indomethacin, and a protein kinase A inhibitor (PKA‐I) on the Cl− conductance in isolated zymogen granules (ZG) from cholecystokinin octapeptide (CCK‐8) pre‐stimulated pancreatic acini. The Cl− conductance in isolated ZG from CCK‐8 pre‐stimulated rat pancreatic acini increases with increasing CCK‐8 concentrations and decreases at supramaximal CCK‐8 concentrations. The basal and CCK‐8‐stimulated Cl− conductance in ZG is inhibited by pretreatment of acini with PGE2 (10−6 M). This PGE2‐induced inhibition is abolished in the presence of PKA‐I (20 U/ml). Furthermore, pretreatment of acini with indomethacin (10−5 M) or PKA‐I (20 U/ml) abolishes the decrease in the Cl− conductance at supramaximal CCK‐8 concentrations (10−9 M). We conclude that the inhibition of the Cl− conductance in isolated ZG at high CCK‐8 concentrations is mediated by an enhanced production of PGE2, and that PGE2 operates by stimulating adenylate cyclase (AC) with a consequent rise in cAMP and activation of PKA.
