Interactions between secretin and acetylcholine in the regulation of fluid secretion by isolated rat pancreatic ducts.

Evans, Richard; Ashton, Nick; Elliott, A.; Green, R; Argent, Barry E.

doi:10.1113/jphysiol.1996.sp021683

Cited by 30 publications

(30 citation statements)

References 34 publications

(69 reference statements)

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“…Activation of tachykinin receptors leads to activation of phospholipase C, followed by the production of inositol 1,4,5-trisphosphate and diacylglycerol, which in turn lead to a rise in intracellular Ca 2ϩ concentration and activation of protein kinase C (PKC), respectively (13). Previously, it has been reported that activation of PKC by phorbol 12,13-dibutyrate can inhibit fluid secretion by rat pancreatic ducts (6), and it is possible that SP exerts its effect on apical anion exchange via PKCmediated phosphorylation.…”

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confidence: 99%

Substance P inhibits bicarbonate secretion from guinea pig pancreatic ducts by modulating an anion exchanger

Hegyi¹,

Gray²,

Argent³

2003

American Journal of Physiology-Cell Physiology

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The stimulatory pathways controlling HCO 3 Ϫ secretion by the pancreatic ductal epithelium are well described. However, only a few data are available concerning inhibitory mechanisms, which may play an important role in the physiological control of the pancreas. The aim of this study was to investigate the cellular mechanism by which substance P (SP) inhibits pancreatic ductal HCO 3 Ϫ secretion. Small intra/interlobular ducts were isolated from the pancreas of guinea pigs. During overnight culture the ducts seal to form a closed sac. Transmembrane HCO 3 Ϫ fluxes were calculated from changes in intracellular pH (measured using the pH-sensitive dye BCECF) and the buffering capacity of the cells. We found that secretin can stimulate HCO 3 Ϫ secretion in guinea pig pancreatic ducts about fivefold and that this effect could be totally blocked by SP. The inhibitory effect of SP was relieved by spantide, an SP receptor antagonist. SP had no effect on the activity of basolateral Na ϩ -HCO 3 Ϫ cotransporters and Na ϩ /H ϩ exchangers. However, the peptide did inhibit a Cl Ϫ -dependent HCO 3

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mentioning

confidence: 99%

Substance P inhibits bicarbonate secretion from guinea pig pancreatic ducts by modulating an anion exchanger

Hegyi¹,

Gray²,

Argent³

2003

American Journal of Physiology-Cell Physiology

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“…Even cholinergic stimulation and CCK can evoke HCO 3 2 secretion in some species, and they can potentiate the secretin effect on the volume of secretion (You et al 1983;Holst 1993;Park et al 1998;Chey and Chang 2001), although there are exceptions (Evans et al 1996). Whether human pancreatic juice is also rich in HCO 3 2 under these conditions is not clear.…”

Section: Regulation Of Pancreatic Duct Secretionmentioning

confidence: 99%

The Cystic Fibrosis of Exocrine Pancreas

Wilschanski

Novak

2013

Cold Spring Harbor Perspectives in Medicine

130

113

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The cystic fibrosis transmembrane conductance regulator (CFTR) protein is highly expressed in the pancreatic duct epithelia and permits anions and water to enter the ductal lumen. This results in an increased volume of alkaline fluid allowing the highly concentrated proteins secreted by the acinar cells to remain in a soluble state. This work will expound on the pathophysiology and pathology caused by the malfunctioning CFTR protein with special reference to ion transport and acid-base abnormalities both in humans and animal models. We will also discuss the relationship between cystic fibrosis (CF) and pancreatitis, and outline present and potential therapeutic approaches in CF treatment relevant to the pancreas.

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“…Importantly, TPA completely inhibited fluid secretion in response to forskolin but had no effect on the accumulation of cAMP in response to this stimulant (13). Thus, like the effect of SP (6), the inhibitory effect of TPA on ductal fluid secretion seems to occur downstream from the generation of cyclic AMP in the intracellular signaling pathway (13). The aims of the present study were 1) to establish the localization of SP in the guinea pig pancreas, 2) to test whether SP uses the PKC signaling pathway, and 3) to establish whether SP inhibits a luminal Cl Ϫ /HCO 3 Ϫ exchanger in the duct cell.…”

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confidence: 96%

“…The phorbol ester 12-Otetradecanoylphorbol 13-acetate (TPA), which activates PKC, inhibits secretin-stimulated fluid secretion from the pancreas in vivo (40). Moreover, TPA and phorbol 12,13-dibutyrate (PDBu) both inhibit fluid secretion from isolated rat pancreatic ducts (13). Importantly, TPA completely inhibited fluid secretion in response to forskolin but had no effect on the accumulation of cAMP in response to this stimulant (13).…”

mentioning

confidence: 99%

“…Moreover, TPA and phorbol 12,13-dibutyrate (PDBu) both inhibit fluid secretion from isolated rat pancreatic ducts (13). Importantly, TPA completely inhibited fluid secretion in response to forskolin but had no effect on the accumulation of cAMP in response to this stimulant (13). Thus, like the effect of SP (6), the inhibitory effect of TPA on ductal fluid secretion seems to occur downstream from the generation of cyclic AMP in the intracellular signaling pathway (13).…”

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confidence: 99%

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Protein kinase C mediates the inhibitory effect of substance P on HCO₃⁻ secretion from guinea pig pancreatic ducts

Hegyi¹,

Rakonczay²,

Tiszlavicz³

et al. 2005

American Journal of Physiology-Cell Physiology

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Ϫ secretion may be physiologically important in terms of limiting the hydrostatic pressure developed within the ducts and in terms of switching off pancreatic secretion after a meal. Substance P (SP) inhibits secretin-stimulated HCO 3Ϫ secretion by modulating a Cl Ϫ -dependent HCO 3 Ϫ efflux step at the apical membrane of the duct cell (Hegyi P, Gray MA, and Argent BE. Am J Physiol Cell Physiol 285: C268 -C276, 2003). In the present study, we have shown that SP is present in periductal nerves within the guinea pig pancreas, that PKC mediates the effect of SP, and that SP inhibits an anion exchanger on the luminal membrane of the duct cell. Secretin (10 nM) stimulated HCO 3 Ϫ secretion by sealed, nonperfused, ducts about threefold, and this effect was totally inhibited by SP (20 nM). Phorbol 12,13-dibutyrate (PDBu; 100 nM), an activator of PKC, reduced basal HCO 3 Ϫ secretion by ϳ40% and totally blocked secretin-stimulated secretion. In addition, bisindolylmaleimide I (1 nM to 1 M), an inhibitor of PKC, relieved the inhibitory effect of SP on secretin-stimulated HCO 3 Ϫ secretion and also reversed the inhibitory effect of PDBu. Western blot analysis revealed that guinea pig pancreatic ducts express the ␣-, ␤ I-, ␦-, ⑀-, -, -, -, and -isoforms of PKC. In microperfused ducts, luminal H 2DIDS (0.5 mM) caused intracellular pH to alkalinize and, like SP, inhibited basal and secretinstimulated HCO 3 Ϫ secretion. SP did not inhibit secretion further when H 2DIDS was present in the lumen, suggesting that SP and H2DIDS both inhibit the activity of an anion exchanger on the luminal membrane of the duct cell.pancreas; Cl Ϫ /HCO 3 Ϫ exchanger; inhibition; epithelium THE PANCREATIC DUCTAL EPITHELIUM secretes an alkaline fluid that may contain up to 140 mM NaHCO 3 (4, 5). While the regulatory pathways that stimulate pancreatic ductal HCO 3 Ϫ secretion have been described well in the literature (4, 5), much less is known about inhibitory pathways. Such inhibitory pathways may be physiologically important in terms of limiting the hydrostatic pressure within the lumen of the duct (thus preventing leakage of enzymes into the parenchyma of the gland) and in terms of switching off pancreatic secretion after a meal (1). Both somatostatin (20, 32) and peptide YY (1, 34) have been shown to inhibit secretion from the intact pancreas and probably work by interfering with the neural and/or hormonal mechanisms that control the gland. In contrast, substance P (SP) (6, 18), 5-hydroxytryptamine (45), arginine vasopressin (29), and basolateral ATP (22) all have been shown to inhibit fluid and/or HCO 3 Ϫ secretion from isolated pancreatic ducts. Therefore, these agents must exert their effects directly on the ductal epithelium.SP has been identified in the pancreas of the dog, rat, and mouse (36), and the peptide has been shown to inhibit secretion from the intact gland of the dog (26, 31) and rat (27). Moreover, SP is a potent inhibitor of basal fluid secretion from isolated rat pancreatic ducts as well as of fluid secretion stimulated by secr...

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Interactions between secretin and acetylcholine in the regulation of fluid secretion by isolated rat pancreatic ducts.

Cited by 30 publications

References 34 publications

Substance P inhibits bicarbonate secretion from guinea pig pancreatic ducts by modulating an anion exchanger

Substance P inhibits bicarbonate secretion from guinea pig pancreatic ducts by modulating an anion exchanger

The Cystic Fibrosis of Exocrine Pancreas

Protein kinase C mediates the inhibitory effect of substance P on HCO₃⁻ secretion from guinea pig pancreatic ducts

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Interactions between secretin and acetylcholine in the regulation of fluid secretion by isolated rat pancreatic ducts.

Cited by 30 publications

References 34 publications

Substance P inhibits bicarbonate secretion from guinea pig pancreatic ducts by modulating an anion exchanger

Substance P inhibits bicarbonate secretion from guinea pig pancreatic ducts by modulating an anion exchanger

The Cystic Fibrosis of Exocrine Pancreas

Protein kinase C mediates the inhibitory effect of substance P on HCO3− secretion from guinea pig pancreatic ducts

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Protein kinase C mediates the inhibitory effect of substance P on HCO₃⁻ secretion from guinea pig pancreatic ducts