醛固酮
布美他尼
内分泌学
内科学
分泌物
化学
上皮钠通道
生物
离子运输机
医学
钠
生物化学
膜
有机化学
作者
Andrew Nickerson,Vazhaikkurichi M. Rajendran
标识
DOI:10.1007/s00018-023-04857-x
摘要
The corticosteroid hormone, aldosterone, markedly enhances K+ secretion throughout the colon, a mechanism critical to its role in maintaining overall K+ balance. Previous studies demonstrated that basolateral NKCC1 was up-regulated by aldosterone in the distal colon specifically to support K+ secretion—which is distinct from the more well-established role of NKCC1 in supporting luminal Cl− secretion. However, considerable segmental variability exists between proximal and distal colonic ion transport processes, especially concerning their regulation by aldosterone. Furthermore, delineating such region-specific effects has important implications for the management of various gastrointestinal pathologies. Experiments were therefore designed to determine whether aldosterone similarly up-regulates NKCC1 in the proximal colon to support K+ secretion. Using dietary Na+ depletion as a model of secondary hyperaldosteronism in rats, we found that proximal colon NKCC1 expression was indeed enhanced in Na+-depleted (i.e., hyperaldosteronemic) rats. Surprisingly, electrogenic K+ secretion was not detectable by short-circuit current (ISC) measurements in response to either basolateral bumetanide (NKCC1 inhibitor) or luminal Ba2+ (non-selective K+ channel blocker), despite enhanced K+ secretion in Na+-depleted rats, as measured by 86Rb+ fluxes. Expression of BK and IK channels was also found to be unaltered by dietary Na+ depletion. However, bumetanide-sensitive basal and agonist-stimulated Cl− secretion (ISC) were significantly enhanced by Na+ depletion, as was CFTR Cl− channel expression. These data suggest that NKCC1-dependent secretory pathways are differentially regulated by aldosterone in proximal and distal colon. Development of therapeutic strategies in treating pathologies related to aberrant colonic K+/Cl− transport—such as pseudo-obstruction or ulcerative colitis—may benefit from these findings.
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