Inhibitory effects of PGE(2) on K(+) currents and Ca(2+) oscillations in rat pancreatic acinar cells.
Prostaglandin E(2) (PGE(2)) inhibits pancreatic enzyme secretion and shows a protective action against pancreatitis. In this study, we tested the effects of PGE(2) on the slowly activating voltage-dependent K(+) channel current ( I(Ks)) and cholecystokinin (CCK)-induced oscillations of cytosolic [Ca(2+)] ([Ca(2+)](i)) in rat pancreatic acini (RPA). I(Ks) in RPA is reportedly augmented by both Ca(2+)- and cAMP-mediated secretagogues. PGE(2) (10(-7) M) decreased the amplitude of I(Ks), an effect that was more prominent following prior stimulation with secretin. The application of the membrane-permeable cAMP analogue 8-Br-cAMP prevented the effect of PGE(2) on I(Ks). The Ca(2+)-mediated augmentation of I(Ks) by ACh was unaffected by pretreatment with PGE(2). Using fura-2 fluorescence ratiometry to assess [Ca(2+)](i), CCK (<or=10(-10) M)-induced Ca(2+) oscillations were observed in RPAs. The amplitude of the Ca(2+) oscillations was decreased by PGE(2), irrespective of the presence of 8-Br-cAMP. RT-PCR analysis showed that RPAs express predominantly the EP3 subtype of the PGE(2) receptor and its splice variants. Enzyme-immunoassay showed that the secretin-induced production of cAMP in RPAs was inhibited by treatment with PGE(2). In summary, PGE(2) acts on the EP3 receptors to antagonize the cAMP-generating effect of secretin, resulting in the decrease of I(Ks). In addition, PGE(2) suppresses CCK-induced Ca(2+) oscillations in a cAMP-independent manner. These effects of PGE(2) may explain the inhibitory action mechanism of PGE(2) in the exocrine pancreas.
Lee
Ji Eun
JE
Department of Physiology, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea.
Kim
Jun Hee
JH
Choi
So-Jung
SJ
Han
Tae-Hee
TH
Uhm
Dae-Yong
DY
Kim
Sung Joon
SJ
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology*; D002766:Cholecystokinin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D010179:Pancreas / Q000502:physiology*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018078:Receptors, Prostaglandin E / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012633:Secretin / Q000494:pharmacology
D018078:Receptors, Prostaglandin E; D012633:Secretin; D002766:Cholecystokinin; D000242:Cyclic AMP; D015232:Dinoprostone; D011188:Potassium