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.
Department of Physiology, Sungkyunkwan University School of Medicine, Suwon 440-746, Korea.
Ji Eun
JE
Lee
Jun Hee
JH
Kim
So-Jung
SJ
Choi
Tae-Hee
TH
Han
Dae-Yong
DY
Uhm
Sung Joon
SJ
Kim
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