Item

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.