Charney Alan N, Egnor Richard W, Steinbrecher Kris A, Cohen Mitchell B
Nephrology Section, VA Medical Center and New York University School of Medicine, 423 E. 23rd Street, New York, NY 10010, USA.
Biochim Biophys Acta. 2004 Mar 17;1671(1-3):79-86. doi: 10.1016/j.bbagen.2004.01.007.
The small and large intestine secrete guanylin, a peptide homologous to heat stable enterotoxin (STa) elaborated by enterotoxigenic Escherichia coli. Guanylin's role in intestinal electrolyte transport was investigated in guanylin-deficient knockout mice and heterozygous littermate controls. Segments of mid-jejunum, distal ileum, and proximal and distal colon were studied in Ussing chambers in HCO3- Ringer under short circuit conditions. We found that (1) under basal conditions, all segments in control and knockout mice absorb Na+, and the knockout mouse proximal colon secretes Cl-; (2) all segments except the jejunum of knockout mice respond by increasing absorption in response to reductions in pH from 7.6 to 7.1; (3) all segments exhibit decreased absorption in response to 1 mM cAMP; (4) the jejunum and ileum of knockout and control mice, and the proximal colon of control mice (but not knockout mice) respond to the mucosal addition of 50 nM STa with decreases in absorption; and (5) mucosal guanylin caused similar decreases in proximal colon absorption in control and guanylin-deficient mice. These findings suggest that guanylin deficiency causes basal Cl- secretion and reduced responsiveness to STa in mouse proximal colon. The effectiveness of guanylin in this segment suggests a difference in the intestinal secretory actions of STa and guanylin.
小肠和大肠分泌鸟苷素，这是一种与产肠毒素大肠杆菌产生的热稳定肠毒素（STa）同源的肽。在鸟苷素缺陷型基因敲除小鼠和杂合子同窝对照小鼠中研究了鸟苷素在肠道电解质转运中的作用。在短路条件下，于碳酸氢根林格液中，在尤斯灌流小室中研究空肠中段、回肠远端以及结肠近端和远端的肠段。我们发现：（1）在基础条件下，对照小鼠和基因敲除小鼠的所有肠段均吸收钠离子，基因敲除小鼠的近端结肠分泌氯离子；（2）除基因敲除小鼠的空肠外，所有肠段在pH值从7.6降至7.1时，吸收均增加；（3）所有肠段在1 mM环磷酸腺苷作用下吸收均减少；（4）基因敲除小鼠和对照小鼠的空肠和回肠，以及对照小鼠（而非基因敲除小鼠）的近端结肠在黏膜添加50 nM STa后吸收减少；（5）黏膜鸟苷素在对照小鼠和鸟苷素缺陷小鼠的近端结肠均引起类似的吸收减少。这些发现表明，鸟苷素缺乏导致小鼠近端结肠基础氯离子分泌以及对STa的反应性降低。鸟苷素在该肠段的作用效果提示STa和鸟苷素在肠道分泌作用方面存在差异。
