Importance of the Vasoactive Intestinal Peptide Receptor in the Stimulation of Cyclic Adenosine 3′,5′-Monophosphate in Gallbladder Epithelial Cells of Man

Dupont, Christophe; Broyart, Jean-Pierre; Broer, Y; Chenut, Bernard; Laburthe, Marc; Rosselin, G

doi:10.1172/jci110091

Cited by 70 publications

(18 citation statements)

References 35 publications

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“…1C). Together with previous physiological studies, 31,32 these results indicate that VIP-induced regulations of bile secretion mainly take place in bile duct and gallbladder epithelial cells.…”

Section: Resultssupporting

confidence: 86%

“…In primary cultures of gallbladder epithelial cells, VIP elicited both cAMP production and chloride secretion. In line with previous studies, [4][5][6]31,32 these observations suggest that VIP through VPAC1 activation is a major regulator of ductular secretion and of cAMP-dependent hydroelectrolytic secretion in the gallbladder.…”

Section: Discussionsupporting

confidence: 91%

“…Whether VIP regulation is mediated by a cAMP pathway in biliary epithelial cell is an issue of conflicting results. 4,31 To address this question, we measured cAMP production and chloride secretion in primary cultures of human gallbladder epithelial cells exposed to VIP. In gallbladder epithelial cells, VIP elicited a dose-dependent increase in cAMP content ( Fig.…”

Section: Resultsmentioning

confidence: 99%

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VPAC1 expression is regulated by FXR agonists in the human gallbladder epithelium

et al. 2005

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Vasoactive intestinal peptide receptor-1 (VPAC1) is the high-affinity receptor of vasoactive intestinal peptide (VIP), a major regulator of bile secretion. To better define the level at which VPAC1 stimulates bile secretion, we examined its expression in the different cell types participating in bile formation (i.e., hepatocytes, bile duct, and gallbladder epithelial cells). Because VPAC1 expression was previously shown to be regulated by nuclear receptors, we tested the hypothesis that it may be regulated by the farnesoid X receptor (FXR). Quantitative RT-PCR and immunoblot analyses of cell isolates indicated that VPAC1 is expressed in all three cell types lining the human biliary tree, with predominant expression in the gallbladder. In primary cultures of human gallbladder epithelial cells, VIP induced cAMP production and chloride secretion. Analysis of the VPAC1 gene revealed the presence of potential FXR response element sequences, and both FXR and RXR␣ expressions were detected in gallbladder epithelial cells. In these cells, the FXR pharmacological agonist GW4064 upregulated VPAC1 expression in a dose-dependent manner, and this effect was antagonized by the RXR␣ ligand, 9-cis retinoic acid. T he regulation of bile secretion occurs at different levels of the biliary tree. Bile is formed primarily in hepatocyte canaculi by an osmotic process resulting from active bile salt secretion. 1 In bile ducts and in the gallbladder, bile is then modified by the absorption or secretion of water and ions. 2,3 Thus, bile delivered to the intestine results from vectorial transport occurring in the different epithelial cell types lining the biliary tree, i.e., hepatocytes, intrahepatic bile duct, and gallbladder epithelial cells. Among regulatory peptides, the vasoactive intestinal peptide (VIP) induces bile secretion by stimulating transport activities both in hepatocytes and in biliary epithelial cells. In hepatocytes, VIP induces an increase in bile salt-dependent bile secretion. 4 In bile ducts, VIP stimulates a bicarbonaterich secretion with higher potency than all other secretagogues, including secretin. 4 In the gallbladder, VIP is also a potent inducer of fluid and anion secretion. 5,6 In most systems, VIP effects are mediated by cyclic adenosine monophosphate (cAMP) production after the activation of highor low-affinity receptors, namely, the vasoactive intestinal peptide receptor-1 (VPAC1) and the vasoactive intestinal peptide receptor-2 (VPAC2), respectively. 7,8 Among these two types of VIP receptors, only VPAC1 is expressed in the liver. 7 In cancer cell lines, VPAC1 gene transcription is regulated by members of the nuclear receptor superfamily. [9][10][11]

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Section: Resultssupporting

confidence: 86%

Section: Discussionsupporting

confidence: 91%

Section: Resultsmentioning

confidence: 99%

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VPAC1 expression is regulated by FXR agonists in the human gallbladder epithelium

et al. 2005

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“…[11][12][13] Both intrahepatic and gallbladder biliary epithelial cells respond to secretin and VIP by an increase in intracellular adenosine 3Ј,5Ј-cyclic monophosphate (cAMP) levels. [14][15][16] Investigation of the gallbladder epithelium may therefore be useful in gaining insight into the mechanisms of fluid secretion not only in the gallbladder, but also in the intrahepatic bile ducts.…”

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confidence: 99%

Regulation of electrogenic anion secretion in normal and cystic fibrosis gallbladder mucosa

et al. 1999

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Fluid and ion transport across biliary epithelium contributes to bile flow. Alterations of this function may explain hepatobiliary complications in cystic fibrosis (CF). We investigated electrogenic anion transport across intact non-CF and CF human gallbladder mucosa in Ussing-type chambers. In non-CF tissues, baseline transmural potential difference (PD), short-circuit current (Isc), and resistance (R) were ؊2.2 ؎ 0.3 mV (lumen negative), 40.7 ؎ 7.8 A/cm 2 , and 66.5 ؎ 9.6 ⍀ · cm 2 , respectively (n ‫؍‬ 14). The addition of forskolin (10 ؊5 mol/L) to the apical and basolateral baths and that of adenosine 5Ј-triphosphate (ATP) (10 ؊4 mol/L) to the apical bath induced significant increases in Isc by 8.0 ؎ 1.4 and 10.3 ؎ 1.8 A/cm 2 , respectively. Depletion of bathing solutions in Cl ؊ and HCO 3 ؊ significantly reduced baseline Isc and the forskolin-and ATPinduced increases in Isc. Anion secretion was stimulated by extracellular ATP via P2Y 2 purinoceptors, as indicated by the effects of different nucleotides on Isc and on 36 Cl efflux in cultured gallbladder epithelial cells. This effect was mediated by cytosolic calcium increase and Ca 2؉ /calmodulindependent protein kinase II, as ascertained by using inhibitors. In CF preparations, basal PD and Isc were lower than in non-CF, and the response to forskolin was abolished, whereas the response to ATP was enhanced (P F .05 for all). We conclude that electrogenic anion secretion occurs in human gallbladder mucosa under basal state and is stimulated by an adenosine 3Ј,5Ј-cyclic monophosphate (cAMP)-dependent pathway mediated by cystic fibrosis transmembrane conductance regulator (CFTR), and by exogenous ATP via a CFTR-independent pathway that is up-regulated in CF and involves P2Y 2 purinoceptors and a calciumdependent pathway. (HEPATOLOGY 1999;29:5-13.)

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“…Moreover, when IBMX was combined with peptone, the CCK response was equal to the sum of the effects of the individual agents. Similarly, in the isolated gall-bladder and intestinal epithelial cell preparation, vasoactive intestinal polypeptide, which is known to activate the adenylate system, stimulated the production of cyclic AMP in an additive manner with low concentrations of IBMX (Laburthe, Prieto, Amiranoff, Dupont, Hui Bon Hoa & Rosselin, 1979; Broyart, Broer, Chenut, Laburthe & Rosselin, 1981). This suggests the possibility that peptone action on release of CCK-LI is mediated via transduction mechanisms dependent on cyclic AMP.…”

Section: Discussionmentioning

confidence: 94%

Role of cyclic nucleotides and calcium in the nutrient‐induced release of cholecystokinin‐like immunoreactivity in rats.

Cuber

Aucouturier

Bernard

et al. 1992

The Journal of Physiology

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SUMMARY1. This study was undertaken with an isolated vascularly perfused rat duodenojejunal preparation to investigate the mechanisms of the release of cholecystokinin measured by immunoassay (cholecystokinin-like immunoreactivity, CCK-LI).2. Intra-arterial infusion of forskolin (2-20 /1M) evoked a prompt and wellsustained secretion of CCK-LI which was increased to a mean value of 600 % of basal with the highest dose tested. 3-Isobutyl-1-methylxanthine (IBMX) (10-6-10-M) stimulated the secretion of CCK-LI (maximal increase of 400% of basal at 10-4 M).3. Intra-arterial infusion of,/-phorbol 12-myristate 13-acetate (5 x 10-7-5 x 106 M) and calcium ionophore A23187 (10-6-10-5 M) alone or in combination provoked only a transient increase in the release of CCK-LI.4. Luminal infusion of a 5 % ovalbumin hydrolysate solution produced an immediate release of CCK-LI followed by a well-sustained secretion at 580 % of basal. Intra-arterial infusion of IBMX (10-5 or 10-4 M) in combination with luminal peptone induced a release of CCK-LI which was equal to the sum of the CCK responses evoked by IBMX and peptone given separately.5. Intra-arterial infusion of EGTA (2 mM) abolished the forskolin-and peptoneinduced CCK secretion while luminal EGTA (2 mM) had no inhibitory effect. Verapamil (5 x 10-5-10-0 M) or nifedipine (10-5-5 X 10-5 M) inhibited the peptoneevoked CCK secretion. A high concentration of trifluoperazine (10-4 M) strongly reduced the release of CCK-LI induced by intraluminal peptone while 10-5 M was ineffective.6. It is concluded that the peptone-induced secretion of CCK-LI involves a cyclic AMP-dependent mechanism and the activation of calcium channels possibly located at the basolateral side of the CCK cell.MS 9315

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Importance of the Vasoactive Intestinal Peptide Receptor in the Stimulation of Cyclic Adenosine 3′,5′-Monophosphate in Gallbladder Epithelial Cells of Man

Cited by 70 publications

References 35 publications

VPAC1 expression is regulated by FXR agonists in the human gallbladder epithelium

VPAC1 expression is regulated by FXR agonists in the human gallbladder epithelium

Regulation of electrogenic anion secretion in normal and cystic fibrosis gallbladder mucosa

Role of cyclic nucleotides and calcium in the nutrient‐induced release of cholecystokinin‐like immunoreactivity in rats.

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