Arn M, Butt G, Lubcke R, Ross I, Grigor M, Warhurst G, Barbezat G
Department of Medicine, Dunedin School of Medicine, University of Otago, New Zealand.
Dig Dis Sci. 2000 Nov;45(11):2100-7. doi: 10.1023/a:1026479505738.
In vitro somatostatin is a potent inhibitor of intestinal ion secretion in animal models and cultured human cell lines, providing a rationale for its use in secretory diarrheas. However, the effects of somatostatin on ion transport in native human colonic epithelium have not been reported. In this study the effects of somatostatin and octreotide on the basal short-circuit current and the cAMP- and Ca2+-stimulated short-circuit current were studied in isolated human colonic mucosa mounted in Ussing chambers. Under basal conditions somatostatin and octreotide (1 micromol/liter) stimulated a small, bumetanide-sensitive increase in short-circuit current. Following stimulation of secretion with prostaglandin E2, somatostatin and octreotide further increased the short-circuit current in a dose dependent fashion (ED50 approximately 10 nmol/liter for both). This stimulation of short-circuit current was not affected by pretreatment of the tissue with basolateral tetrodotoxin (1 micromol/liter) or mucosal amiloride (10 micromol/liter). In contrast, somatostatin and octreotide had no effect when secretion was stimulated with 8-bromo-cAMP, and pretreatment of the tissue with somatostatin and octreotide (0.1 micromol/liter) did not alter the secretory response to carbachol. The absence of any inhibitory effect of somatostatin and octreotide on electrogenic secretion in the human colon may explain the variable results obtained when somatostatin or octreotide are used for the treatment of secretory diarrheas.
在动物模型和培养的人细胞系中，体外实验显示生长抑素是肠道离子分泌的强效抑制剂，这为其用于分泌性腹泻的治疗提供了理论依据。然而，生长抑素对人天然结肠上皮离子转运的影响尚未见报道。在本研究中，将分离的人结肠黏膜置于Ussing小室中，研究了生长抑素和奥曲肽对基础短路电流以及环磷酸腺苷（cAMP）和钙离子（Ca2+）刺激的短路电流的影响。在基础条件下，生长抑素和奥曲肽（1微摩尔/升）刺激短路电流出现小幅度、布美他尼敏感的增加。在用前列腺素E2刺激分泌后，生长抑素和奥曲肽以剂量依赖方式进一步增加短路电流（两者的半数有效剂量[ED50]约为10纳摩尔/升）。这种对短路电流的刺激不受用基底外侧河豚毒素（1微摩尔/升）或黏膜阿米洛利（10微摩尔/升）预处理组织的影响。相反，用8-溴-cAMP刺激分泌时，生长抑素和奥曲肽没有作用，并且用生长抑素和奥曲肽（0.1微摩尔/升）预处理组织不会改变对卡巴胆碱的分泌反应。生长抑素和奥曲肽对人结肠电分泌没有任何抑制作用，这可能解释了使用生长抑素或奥曲肽治疗分泌性腹泻时得到的不同结果。
