Effects of phorbol esters and secretin on pancreatic juice secretion in the anaesthetized rat

Salido, Ginés M.; Francis, LP; Camello, Pedro J.; Singh, Jaipaul; Madrid, J.A.; Pariente, José A.

doi:10.1016/0306-3623(90)90699-m

Cited by 16 publications

(11 citation statements)

References 17 publications

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“…Moreover, activation of PKC can inhibit pancreatic secretion. The PKC activator TPA inhibits secretin-stimulated fluid secretion from the pancreas in vivo (40), and both TPA and PDBu inhibit fluid secretion from isolated rat pancreatic ducts (13). Interestingly, it was recently reported that PKC plays a role in the inhibition of secretin-stimulated HCO 3 Ϫ secretion from rat bile ducts, a tissue that has many similarities to the pancreatic duct (17).…”

Section: Inhibitory Effect Of Substance P Is Mediated By Pkcmentioning

confidence: 99%

“…Previously, it was reported that activation of PKC can inhibit pancreatic secretion. 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).…”

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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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Section: Inhibitory Effect Of Substance P Is Mediated By Pkcmentioning

confidence: 99%

mentioning

confidence: 99%

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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“…In several instances, workers have reported either a potentiation or an attenuation of secretory parameters between secretagogues (Jensen & Gardner, 1981;Singh, 1985;Ansah, Dho & Case, 1986;Willems, Van Nooij, Haenen & De Pont, 1987;Rosh, Schusdziarra, Wolf & Classen, 1989;Salido, Francis, Camello, Singh, Madrid & Pariente, 1990;Singh, Lennard, Salido, Wisdom, Render, Pozo & Pariente, 1992). However, no study has hitherto demonstrated any interaction between the gut hormones and activation of intrinsic secretomotor nerves in the regulation of exocrine pancreatic secretion.…”

Section: Introductionmentioning

confidence: 99%

Interaction between secretin and nerve‐mediated amylase secretion in the isolated exocrine rat pancreas

Wisdom¹,

Camello²,

Salido³

et al. 1994

Experimental Physiology

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SUMMARYThis study investigates the effects of the gut peptide, secretin, on nerve-mediated and acetylcholine-evoked amylase secretion and calcium (Ca2") and magnesium (Mg2") mobilization in the in vitro rat pancreas. Both electrical field stimulation (EFS; 50 V, 20 Hz, 1 ms) and acetylcholine (ACh; 10-6 M) caused marked increases in amylase output in isolated pancreatic segments. These responses were inhibited by atropine (10-`M). Secretin (10-'°and 108 M) evoked only a small increase in amylase secretion, which was unaffected by atropine. Combining either EFS or ACh with secretin resulted in an attenuation in amylase output compared with the response obtained with either EFS or ACh alone. In a Mg2"-free medium, secretin failed to inhibit the amylase output evoked by EFS. When forskolin (10-5M) was combined with EFS there was a marked potentiation of amylase output. In fura-2-loaded acinar cells, ACh (10-6 M)

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“…Studies with ion replacement (gluconate for chloride) and furosemide indicated that the basal and Interactions between cholecystokinin and phorbol ester in the pancreas of the anaesthetized rat and permeabilized acini BY L. P. FRANCIS*, P. J. CAMELLO, J. SINGH*, G. M. SALIDO The phorbol ester, 12-O-tetradecanoyl-phorbol-13-acetate (TPA) can stimulate both secretary rate and total protein output in the pancreas of the anaesthetized rat. When combined with secretin, TPA caused a marked reduction in pancreatic juice flow compared to secretin alone (Salido et al 1990). This study now investigates any possible interactions between TPA and cholecystokinin-octapeptide (CCK-8) on exocrine pancreatic secretion of the anaesthetized rat and isolated permeabilized pancreatic acini.…”

Section: Pmentioning

confidence: 99%

“…The right carotid artery and left jugular vein were cannulated to measure systemic blood pressure and for injections. The common bile pancreatic duct was cannulated at the entrance to the duodenum for the collection of pancreatic juice by a well established method (Salido et al 1990). For the in vitro experiments young rats (150-200 g) of either sex were killed by cervical dislocation.…”

Section: Pmentioning

confidence: 99%

Proceedings of the Physiological Society, 30‐31 March 1990,University College London Meeting: Communications

1990

The Journal of Physiology

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Effects of phorbol esters and secretin on pancreatic juice secretion in the anaesthetized rat

Cited by 16 publications

References 17 publications

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

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

Interaction between secretin and nerve‐mediated amylase secretion in the isolated exocrine rat pancreas

Proceedings of the Physiological Society, 30‐31 March 1990,University College London Meeting: Communications

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Effects of phorbol esters and secretin on pancreatic juice secretion in the anaesthetized rat

Cited by 16 publications

References 17 publications

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

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

Interaction between secretin and nerve‐mediated amylase secretion in the isolated exocrine rat pancreas

Proceedings of the Physiological Society, 30‐31 March 1990,University College London Meeting: Communications

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

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