PGE2 regulates cholecystokinin-octapeptide (CCK-8)-stimulated Cl- conductance in isolated zymogen granules from rat pancreas.
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.
Plusczyk
T
T
Max-Planck-Institut für Biophysik, Frankfurt am Main, Germany.
Piiper
A
A
Schulz
I
I
D000818:Animals; D018118:Chloride Channels; D002712:Chlorides / Q000378:metabolism*; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000502:physiology*; D015232:Dinoprostone / Q000494:pharmacology*; D007213:Indomethacin / Q000494:pharmacology; D007473:Ion Channels / Q000502:physiology; D007700:Kinetics; D008297:Male; D008565:Membrane Proteins / Q000187:drug effects / Q000502:physiology*; D008954:Models, Biological; D010179:Pancreas / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012844:Sincalide / Q000494:pharmacology*
D018118:Chloride Channels; D002712:Chlorides; D007473:Ion Channels; D008565:Membrane Proteins; D015232:Dinoprostone; D012844:Sincalide; D007213:Indomethacin