Carbonic anhydrase isozyme-II-deficient mice lack the duodenal bicarbonate secretory response to prostaglandin E ₂

Abstract

Duodenal bicarbonate secretion (DBS) is accepted as the primary mucosal defense against acid discharged from the stomach and is impaired in patients with duodenal ulcer disease. The secretory response to luminal acid is the main physiological stimulus for DBS and involves mediation by PGE 2 produced by mucosal cells. The aim of this investigation is to elucidate the role of carbonic anhydrases (CAs) II and IX in PGE 2-mediated bicarbonate secretion in the murine duodenum. CA II-and IX-deficient mice and different combinations of their heterozygous and WT counterparts were studied. A 10-mm segment of the proximal duodenum with intact blood supply was isolated, and DBS was titrated by pH-stat (TitroLine-easy, Schott, Mainz, Germany). Mean arterial blood pressure (MAP) was continuously recorded, and blood acid͞base balance and gastrointestinal morphology were analyzed. The duodenal segment spontaneously secreted HCO 3 ؊ at a steady basal rate of 5.3 ؎ 0.6 mol⅐cm ؊1 ⅐h ؊1 . Perfusing the duodenal lumen for 20 min with 47 M PGE2 caused a significant increase in DBS to 13.0 ؎ 2.9 mol⅐cm ؊1 ⅐h ؊1 , P < 0.0001. The DBS response to PGE2 was completely absent in Car2 ؊/؊ mice, whereas basal DBS was normal. The CA IX-deficient mice with normal Car2 alleles showed a slight increase in DBS. Histological abnormalities were observed in the gastroduodenal epithelium in both CA II-and IX-deficient mice. Our data demonstrate a gastrointestinal phenotypic abnormality associated with CA II deficiency. The results show that the stimulatory effect of the duodenal secretagogue PGE 2 completely depends on CA II. duodenal mucosal protection ͉ gastroduodenal histological abnormalities ͉ gastrointestinal phenotype

Data Mining FAERS to Analyze Molecular Targets of Drugs Highly Associated with Stevens-Johnson Syndrome

“…In a study of preeclampsia, anti-CAII antibodies correlated with increased levels of oxidant stress [46]. CAIIdeficient mice develop duodenal ulcers secondary to impaired PGE2 signaling [47]. Carbonic anhydrase I has a role in epithelial regeneration in a mouse colitis inflammation model [48].…”

Parathyroid hormone (PTH) rapidly enhances CFTR-mediated HCO3− secretion in intestinal epithelium-like Caco-2 monolayer: a novel ion regulatory action of PTH

“…In most epithelia, the sources of HCO 3 Ϫ for apical efflux were derived from the basolateral NBCe1-mediated HCO 3 Ϫ uptake and carbonic anhydrase-mediated intracellular HCO 3 Ϫ production (32,36). As shown in Fig.…”

“…The basolateral influx of Cl Ϫ occurs through Na ϩ -K ϩ -2Cl Ϫ cotransporter (NKCC)-1, whereas that of HCO 3 Ϫ may be achieved either by the cytoplasmic carbonic anhydrase-mediated production from CO 2 (36) or the basolateral uptake via NBCe1 (32). NHE was also essential for the extrusion of H ϩ produced by carbonic anhydrase (5,52).…”

CFTR is restricted to a small population of high expresser cells that provide a forskolin-sensitive transepithelial Cl– conductance in the proximal colon of the possum,Trichosurus vulpecula

“…In a number of intestinal epithelia, HCO 3 -secretion results from the hydration of CO 2 by carbonic anhydrase (Knutson et al, 1995;Leppilampi et al, 2005). To determine whether this was operating in the possum proximal colon, paired tissues were pre-treated with mucosal amiloride and serosal bumetanide and then one was incubated with acetazolamide (1mmoll -1 , mucosal and serosal) for 30min before stimulation of both tissues with forskolin.…”