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PGE 2 regulates cholecystokinin‐octapeptide (CCK‐8)‐stimulated Cl − conductance in isolated zymogen granules from rat pancreas
Author(s) -
Plusczyk Thorsten,
Piiper Albrecht,
Schulz Irene
Publication year - 1991
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(91)81392-l
Subject(s) - cholecystokinin , zymogen , pancreas , chemistry , conductance , medicine , endocrinology , biochemistry , biology , enzyme , physics , receptor , condensed matter physics
In this study we have examined the effects of prostaglandin E 2 (PGE 2 ), 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 PGE 2 (10 −6 M). This PGE 2 ‐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 PGE 2 , and that PGE 2 operates by stimulating adenylate cyclase (AC) with a consequent rise in cAMP and activation of PKA.