Carbonic anhydrase isozyme-II-deficient mice lack the duodenal bicarbonate secretory response to prostaglandin E2
Carbonic anhydrase isozyme-II-deficient mice lack the duodenal bicarbonate secretory response to prostaglandin E2
复制标题
DOI：
10.1073/pnas.0508007102
复制
发表时间：
2005-10-18
影响因子：
11.1
通讯作者：
Sjöblom, M
中科院分区：
文献类型：
--
作者：
Leppilampi, M;Parkkila, S;Sjöblom, M
十二指肠碳酸氢盐分泌（DBS）被认为是防止胃酸排出的主要粘膜防御，在十二指肠溃疡患者中受到损害。对鲁米酸的分泌反应是DIBS的主要生理刺激，涉及粘膜细胞产生的PGE(2)介导。本研究的目的是阐明碳酸酐酶（CAs） II和IX在PGE(2)介导的小鼠十二指肠碳酸氢盐分泌中的作用。研究了caii和ix缺陷小鼠及其杂合子和WT对应物的不同组合。分离出血供完整的十二指肠近端10mm段，用pH-stat滴定DBS （TitroLine-easy, Schott, Mainz, Germany）。连续记录平均动脉血压（MAP），分析血酸碱平衡及胃肠道形态。十二指肠段以5.3 +/- 0.6 μ mol中心点cm（-1）中心点h（-1）的稳定基础速率自发分泌HCO3-。47 μ M PGE(2)灌注十二指肠管腔20 min后，DBS显著升高至13.0 +/- 2.9 μ mol中心dot cm（-1）中心dot h(-1), P < 0.0001。Car2（-/-）小鼠对PGE(2)的DBS反应完全缺失，而基础DBS是正常的。具有正常Car2等位基因的CA ix缺陷小鼠的DBS略有增加。caii和ix缺陷小鼠胃十二指肠上皮均出现组织学异常。我们的数据表明，胃肠道表型异常与钙II缺乏症有关。结果表明，十二指肠促分泌剂PGE(2)的刺激作用完全依赖于CA II。
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 DIBS 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 acid/base balance and gastrointestinal morphology were analyzed. The duodenal segment spontaneously secreted HCO3- at a steady basal rate of 5.3 +/- 0.6 mu mol center dot cm(-1)center dot h(-1). Perfusing the duodenal lumen for 20 min with 47 mu M PGE(2) caused a significant increase in DBS to 13.0 +/- 2.9 mu mol center dot cm(-1)center dot h(-1), P < 0.0001. The DBS response to PGE(2) 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.