Inhibitory effects of PGE 2 on K + currents and Ca 2+ oscillations in rat pancreatic acinar cells

Abstract

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.

TLQP-21, a VGF-derived peptide, stimulates exocrine pancreatic secretion in the rat

“…The experimental model used does not permit us to establish the exact site of action of PGs. However, pancreatic acini cannot be considered as a target of PGs stimulatory effect, as it is known that on acinar cells PGs have no role [11] or an inhibitory effect on CCK-stimulated pancreatic secretion [19]. It has been reported by other authors, that PGE 2 stimulate protein secretion from exocrine pancreas by regulating the tone of pancreatic ducts which plays an important role in directing and moving the secretory products out of the tissue and preventing reflux of bile salts and intestinal materials in the pancreas [22].…”

Chloride Selective Calix[4]arene Optical Sensor Combining Urea Functionality with Pyrene Excimer Transduction

“…The combination of molecular platforms with (thio)urea functionality crowned with fluorescent signal transduction provides the basis for powerful optical sensors for anions and has recently received much interest among researchers. ,− Fluorescent moieties available to the scientist are typically aromatics such as substituted benzenes, anthracenes, naphthalenes, and pyrenes. Pyrenes are a particularly elegant basis for ratiometric based optical sensors, where the ratio of two emission wavelengths comprise the analytical signal. , To date the pyrene Excimer/monomer system has been exploited mainly for cation sensing − and increasingly for anion sensing. − To the best of our knowledge, there are few examples where pyrene and (thio)urea systems have been proximally combined in anion host compounds and none based on a calixarene platform. , …”

“…Pyrenes are a particularly elegant basis for ratiometric based optical sensors, where the ratio of two emission wavelengths comprise the analytical signal 57,58 . To date the pyrene Excimer/monomer system has been exploited mainly for cation sensing [59][60][61][62][63][64][65][66][67][68][69][70] and increasingly for anion sensing [71][72][73][74] . To the best of our knowledge there are few examples where pyrene and (thio)urea systems have been proximally combined in anion host compounds and none based on a calixarene platform 75,76 .…”