Somatostatin peptides inhibit basolateral potassium channels in human colonic crypts
Somatostatin peptides inhibit basolateral potassium channels in human colonic crypts
复制标题
DOI：
10.1152/ajpgi.1999.277.5.g967
复制
发表时间：
1999-11-01
影响因子：
4.5
通讯作者：
Lomax, RB
中科院分区：
文献类型：
--
作者：
Sandle, GI;Warhurst, G;Lomax, RB
生长抑素是一种有效的肠道Cl-分泌抑制剂。我们使用膜片钳记录技术来研究生长抑素对基底外侧低电导（23-pS） K+通道的影响。它是人结肠隐窝分泌Cl-过程的重要组成部分。生长抑素（2 μ M）可引起未受刺激隐窝细胞附着斑块中“自发”K+通道活性下降约80%（50%的抑制作用=类似于8分钟），这是电压无关的，可以通过百日咳毒素（200 ng/ml）预处理隐窝18小时来阻止，暗示G蛋白依赖机制。在受100-200 μ M二丁基cAMP刺激的隐窝中，2 μ M生长抑素及其合成类似物奥曲肽（2 μ M）均产生与未受刺激的隐窝相似程度的K+通道抑制，这种抑制在低cl - (5 mM)条件下也存在。此外，2 μ M生长抑素可以消除2 μ M thapsigargin刺激的K+通道活性增加，但对thapsigargin刺激的细胞内Ca2+升高没有影响。这些结果表明，生长抑素肽通过G蛋白依赖机制抑制人结肠隐窝细胞的23-pS基底外侧K+通道，这可能导致通道固有的Ca2+敏感性丧失。
Somatostatin is a powerful inhibitor of intestinal Cl- secretion. We used patch-clamp recording techniques to investigate the effects of somatostatin on low-conductance (23-pS) K+ channels in the basolateral. membrane of human colonic crypts, which are an important component of the Cl- secretory process. Somatostatin (2 mu M) elicited a >80% decrease in "spontaneous" K+ channel activity in cell-attached patches in nonstimulated crypts (50% inhibition =similar to 8 min), which was voltage-independent and was prevented by pretreating crypts for 18 h with pertussis toxin (200 ng/ml), implicating a G protein-dependent mechanism. In crypts stimulated with 100-200 mu M dibutyryl cAMP, 2 mu M somatostatin and its synthetic analog octreotide (2 mu M) both produced similar degrees of K+ channel inhibition to that seen in nonstimulated crypts, which was also present under low-Cl- (5 mM) conditions. In addition, 2 mu M somatostatin abolished the increase in K+ channel activity stimulated by 2 mu M thapsigargin but had no effect on the thapsigargin-stimulated rise in intracellular Ca2+. These results indicate that somatostatin peptides inhibit 23-pS basolateral K+ channels in human colonic crypt cells via a G protein-dependent mechanism, which may result in loss of the channel's inherent Ca2+ sensitivity.