Fluid Transfer in the Everted Human Gallbladder *

Onstad, Gerald R.; Schoenfield, Leslie J.; Higgins, John A.

doi:10.1172/jci105562

Cited by 31 publications

(6 citation statements)

References 21 publications

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“…9 Significant variations in the ion transport properties of the gallbladder epithelium according to species have also been reported. 40 The human gallbladder mucosa spontaneously generates a lumen-negative PD, as shown in previous records 41,42 and in the present study. We herein provide evidence that the PD across human gallbladder mucosa is predominantly a result of transepithelial electrogenic anion secretion.…”

Section: Discussionsupporting

confidence: 89%

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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Section: Discussionsupporting

confidence: 89%

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

et al. 1999

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“…However, because it is known that net water transport derives from the balance of both mucosal-to-serosa and serosal-tomucosa movements, when a serosal-to-mucosa hydrostatic gradient is present, as in our preparation, fluid net secretion in the lumen occurs. 25,26 In pigs in vivo, a gallbladder intraluminal pressure of approximately 7 cm H 2 0 counteracts the hydrodynamic pressure caused by blood flow. 27 Under our in vitro experimental conditions, intraluminal pressure was always lower than 0.5 cm H 2 0.…”

Section: Discussionmentioning

confidence: 99%

The human gallbladder increases cholesterol solubility in bile by differential lipid absorption: A study using a newin vitro model of isolated intra-arterially perfused gallbladder

Corradini¹,

Ripani²,

Guardia³

et al. 1998

Hepatology

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In this study, we first developed and validated a new in vitro isolated, intra-arterially perfused, gallbladder model and then applied the method to investigate the absorption of biliary lipids by the gallbladder wall and the effect of this process on the composition of human bile. Oxygenated and glucose-added buffer was perfused through the cystic artery to maintain organ viability. A standard pooled natural bile, radiolabeled with H3-cholesterol and C14-palmitoyl-linoleoyl-phosphatidylcholine, was instilled in the lumen via a cystic duct catheter. Changes in bile volume and lipid concentrations were monitored at time intervals to evaluate the disappearance of lipids from bile caused by gallbladder absorptive function. Organ viability was demonstrated by stable lactate dehydrogenase (LDH) organ release and oxygen consumption throughout the experiments. In the pig, disappearance rates of lipids from bile were similar in vitro and in vivo, demonstrating the validity of the isolated in vitro model for functional studies. By applying our in vitro isolated preparation to the human gallbladder, we found that 23% of cholesterol and 32% of phosphatidylcholine, but only 9% of bile salts, disappeared from bile in 5 hours. As a consequence, at the end of the experiments, cholesterol (P < .05) and phospholipid (P < .05) molar percentages were significantly reduced, while the bile salt (P < .05) molar percentage was significantly increased with respect to values at the beginning of the studies. Our findings are of pathophysiological relevance and support the concept that the human gallbladder modifies the relative composition of biliary lipids in such a way as to increase cholesterol solubility in bile.

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“…Cholecystokinin-pancreozymin ( CCK-PZ) causes contraction of the human gallbladder in vivo (1,2 ) and in vitro (3) but the influence, if any, of other gastrointestinal hormones on the organ is unknown. The Cterminal tetrapeptide of CCK-PZ may be identical with that part of the gastrin molecule (4, 5) which increases antral motility.…”

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confidence: 99%

“…Evidence has been advanced indicating that prolonged elevation of serum amylase activity may result from the existence in the serum of a macromolecule of amylase that is too large to be excreted by the kidneys (1)(2)(3)(4). Certain observations made on the nature of this large amylase structure constitute the basis of the present report.…”

mentioning

confidence: 99%

Effect of Cholecystokinin, Gastrin, Secretin, and Glucagon on Human Gallbladder Muscle in Vitro

Cameron¹,

Phillips²,

Summerskill³

1969

Experimental Biology and Medicine

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Fluid Transfer in the Everted Human Gallbladder *

Cited by 31 publications

References 21 publications

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

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

The human gallbladder increases cholesterol solubility in bile by differential lipid absorption: A study using a newin vitro model of isolated intra-arterially perfused gallbladder

Effect of Cholecystokinin, Gastrin, Secretin, and Glucagon on Human Gallbladder Muscle in Vitro

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