Inhibitory effects of PGE2 on K+ currents and Ca2+ oscillations in rat pancreatic acinar cells

Ji Eun Lee, Jun Hee Kim, So Jung Choi, Tae Hee Han, Dae Yong Uhm, Sung Joon Kim

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

Prostaglandin E2 (PGE2) inhibits pancreatic enzyme secretion and shows a protective action against pancreatitis. In this study, we tested the effects of PGE2 on the slowly activating voltage-dependent K+ channel current (IKs) and cholecystokinin (CCK)-induced oscillations of cytosolic [Ca2+] ([Ca2+]i) in rat pancreatic acini (RPA). IKs in RPA is reportedly augmented by both Ca2+- and cAMP-mediated secretagogues. PGE2 (10-7 M) decreased the amplitude of IKs, 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 PGE2 on IKs. The Ca2+-mediated augmentation of IKs by ACh was unaffected by pretreatment with PGE2. Using fura-2 fluorescence ratiometry to assess [Ca2+]i, CCK (≤10-10 M)-induced Ca2+ oscillations were observed in RPAs. The amplitude of the Ca2+ oscillations was decreased by PGE2, irrespective of the presence of 8-Br-cAMP. RT-PCR analysis showed that RPAs express predominantly the EP3 subtype of the PGE2 receptor and its splice variants. Enzyme-immunoassay showed that the secretin-induced production of cAMP in RPAs was inhibited by treatment with PGE2. In summary, PGE2 acts on the EP3 receptors to antagonize the cAMP-generating effect of secretin, resulting in the decrease of IKs. In addition, PGE2 suppresses CCK-induced Ca2+ oscillations in a cAMP-independent manner. These effects of PGE2 may explain the inhibitory action mechanism of PGE2 in the exocrine pancreas.

Original languageEnglish (US)
Pages (from-to)619-626
Number of pages8
JournalPflugers Archiv European Journal of Physiology
Volume444
Issue number5
DOIs
StatePublished - Dec 28 2002
Externally publishedYes

Keywords

  • Acinar cell
  • Ca oscillations
  • Cholecystokinin
  • EP receptor
  • K channel
  • Pancreas
  • Prostaglandin E
  • RT-PCR
  • cAMP

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Physiology (medical)

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