title: Duodenal acidity "sensing" but not epithelial HCO3- supply is critically dependent on carbonic anhydrase II expression.
abstract: Carbonic anhydrase (CA) is strongly expressed in the duodenum and has been implicated in a variety of physiological functions including enterocyte HCO(3)(-) supply for secretion and the "sensing" of luminal acid and CO(2). Here, we report the physiological role of the intracellular CAII isoform involvement in acid-, PGE(2,) and forskolin-induced murine duodenal bicarbonate secretion (DBS) in vivo. CAII-deficient and WT littermates were studied in vivo during isoflurane anesthesia. An approximate 10-mm segment of the proximal duodenum with intact blood supply was perfused under different experimental conditions and DBS was titrated by pH immediately. Two-photon confocal microscopy using the pH-sensitive dye SNARF-1F was used to assess duodenocyte pH(i) in vivo. After correction of systemic acidosis by infusion of isotonic Na(2)CO(3), basal DBS was not significantly different in CAII-deficient mice and WT littermates. The duodenal bicarbonate secretory response to acid was almost abolished in CAII-deficient mice, but normal to forskolin- or 16,16-dimethyl PGE(2) stimulation. The complete inhibition of tissue CAs by luminal methazolamide and i.v. acetazolamide completely blocked the response to acid, but did not significantly alter the response to forskolin. While duodenocytes acidified upon luminal perfusion with acid, no significant pH(i) change occurred in CAII-deficient duodenum in vivo. The results suggest that CA II is important for duodenocyte acidification by low luminal pH and for eliciting the acid-mediated HCO(3)(-) secretory response, but is not important in the generation of the secreted HCO(3)(-) ions.
authors.affiliation: Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover 30625, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Sjöblom
authors.forename: Anurag Kumar
authors.initials: AK
authors.lastname: Singh
authors.forename: Wen
authors.initials: W
authors.lastname: Zheng
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
authors.forename: Bi-guang
authors.initials: BG
authors.lastname: Tuo
authors.forename: Anja
authors.initials: A
authors.lastname: Krabbenhöft
authors.forename: Brigitte
authors.initials: B
authors.lastname: Riederer
authors.forename: Gerolf
authors.initials: G
authors.lastname: Gros
authors.forename: Ursula
authors.initials: U
authors.lastname: Seidler
mesh_terms: D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000086:Acetazolamide / Q000494:pharmacology; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism*; D002245:Carbon Dioxide / Q000378:metabolism; D024402:Carbonic Anhydrase II / Q000037:antagonists & inhibitors / Q000502:physiology*; D005576:Colforsin / Q000494:pharmacology; D004386:Duodenum / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008704:Methazolamide / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D001639:Bicarbonates; D002245:Carbon Dioxide; D005576:Colforsin; D024402:Carbonic Anhydrase II; D015064:16,16-Dimethylprostaglandin E2; D000086:Acetazolamide; D008704:Methazolamide