Identification of transport abnormalities in duodenal mucosa and duodenal enterocytes from patients with cystic fibrosis

Pratha, Vijaya S.; Hogan, Daniel L.; Martensson, Birgitta; Bernard, J. L.; Zhou, Rulong; Isenberg, Jon I.

doi:10.1016/s0016-5085(00)70358-1

Cited by 95 publications

(103 citation statements)

References 38 publications

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“…The absence of bicarbonate exit might reset intracellular buffering at a higher level, protecting the cells from acidification due to acid loads. This contention is substantiated by the observation that duodenal epithelial cells obtained from patients with cystic fibrosis (CF) have impaired pH i recovery from alkaline loads in chloride-free medium (50). Furthermore, our results are also consistent with the presence of a CFTRlike, NPPB-sensitive bicarbonate-selective anion channel in the apical membrane, as has been described recently for guinea pig gallbladder (51).…”

Section: Figuresupporting

confidence: 90%

Cellular bicarbonate protects rat duodenal mucosa from acid-induced injury

Akiba¹,

Furukawa²,

Guth³

et al. 2001

J. Clin. Invest.

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Section: Figuresupporting

confidence: 90%

Cellular bicarbonate protects rat duodenal mucosa from acid-induced injury

Akiba¹,

Furukawa²,

Guth³

et al. 2001

J. Clin. Invest.

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“…Strikingly, the phenotype of the pancreas, perhaps the most acknowledged organ of HCO 3 -transport, segregates well with genotypes that severely disrupt CFTR-dependent HCO 3 transport in this organ and in the sweat duct (15,17). Likewise, HCO 3 -secretion is reduced in the CF intestine (16,18,19). More-over, experimentally altering HCO 3 -secretion appeared to change mucus consistency in submucosal gland secretion in sheep, pigs, and human trachea (20).…”

Section: Introductionmentioning

confidence: 95%

Normal mouse intestinal mucus release requires cystic fibrosis transmembrane regulator–dependent bicarbonate secretion

García

Yang²,

Quinton³

2009

J. Clin. Invest.

256

239

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The mechanisms underlying mucus-associated pathologies in cystic fibrosis (CF) remain obscure. However, recent studies indicate that CF transmembrane conductance regulator (CFTR) is required for bicarbonate (HCO 3 -) transport and that HCO 3 -is critical for normal mucus formation. We therefore investigated the role of HCO 3 -in mucus secretion using mouse small intestine segments ex vivo. Basal rates of mucus release in the presence or absence of HCO 3 -were similar. However, in the absence of HCO 3 -, mucus release stimulated by either PGE 2 or 5-hydroxytryptamine (5-HT) was approximately half that stimulated by these molecules in the presence of HCO 3 -. Inhibition of HCO 3 -and fluid transport markedly reduced stimulated mucus release. However, neither absence of HCO 3 -nor inhibition of HCO 3 -transport affected fluid secretion rates, indicating that the effect of HCO 3 -removal on mucus release was not due to decreased fluid secretion. In a mouse model of CF (mice homozygous for the most common human CFTR mutation), intestinal mucus release was minimal when stimulated with either PGE 2 or 5-HT in the presence or absence of HCO 3 -. These data suggest that normal mucus release requires concurrent HCO 3 -secretion and that the characteristically aggregated mucus observed in mucin-secreting organs in individuals with CF may be a consequence of defective HCO 3 -transport.

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“…Further, 115 mM luminal HCO 3 -greatly increased granule area in the Cftr-KO goblet cell, which was reminiscent of the early stages of CCH stimulation. Given the deficits of HCO 3 -secretion in the Cftr-KO intestine (50,64,65), losing local HCO 3 -stimulation may contribute to goblet cell enlargement with stored granules, which is often noted in histological sections of CF epithelia. Despite the positive effects of 115 mM HCO 3 -luminal superfusion, goblet cell dysfunction was still apparent in the Cftr-KO enteroids.…”

Section: Discussionmentioning

confidence: 99%