Donowitz M, Levin S, Powers G, Elta G, Cohen P, Cheng H
Gastroenterology. 1985 Oct;89(4):858-66. doi: 10.1016/0016-5085(85)90584-0.
The effects of calcium channel blockers on water transport in the rat ileum and distal colon were studied in vivo using the single-pass perfusion technique. Parenteral but not intraluminal verapamil, and parenteral nifedipine increased ileal water absorption, with effects lasting at least 60 min. In contrast, i.p. verapamil had no effect on rat distal colonic water absorption, whereas intraluminal verapamil significantly stimulated colonic water absorption. Similarly, perfusing the rat descending colon with low-Ca2+ Ringer's-HCO3 stimulated colonic water absorption. Verapamil was not antisecretory because the theophylline-induced decrease in ileal water transport was similar in control animals and in animals pretreated with i.p. verapamil. In addition, nifedipine stimulated active Na and Cl absorption in rabbit ileum. These studies demonstrate that the Ca2+ channel blockers verapamil and nifedipine stimulate basal absorption of water in rat ileum and distal colon in vivo, and stimulate active Na and Cl absorption in rabbit ileum in vitro. The verapamil stimulation of colonic water absorption from the luminal surface was duplicated by perfusion with a low-Ca2+ bathing solution. This suggests the presence of apical membrane Ca2+ channels in rat colon, which appear to be involved in regulation of basal water transport, and that these Ca2+ channels are in a partially open state under basal conditions. Because verapamil stimulates absorption systemically (ileum) as well as intraluminally (colon), Ca2+ channel blockers have properties that might be useful in treatment of diarrheal diseases.
采用单通道灌注技术在体内研究了钙通道阻滞剂对大鼠回肠和远端结肠水转运的影响。静脉注射而非肠腔内注射维拉帕米以及静脉注射硝苯地平可增加回肠水吸收，其作用至少持续60分钟。相比之下，腹腔注射维拉帕米对大鼠远端结肠水吸收无影响，而肠腔内注射维拉帕米可显著刺激结肠水吸收。同样，用低钙林格氏碳酸氢盐溶液灌注大鼠降结肠可刺激结肠水吸收。维拉帕米并无抗分泌作用，因为在对照动物和腹腔注射维拉帕米预处理的动物中，茶碱诱导的回肠水转运减少情况相似。此外，硝苯地平可刺激兔回肠中钠和氯的主动吸收。这些研究表明，钙通道阻滞剂维拉帕米和硝苯地平在体内可刺激大鼠回肠和远端结肠的基础水吸收，并在体外刺激兔回肠中钠和氯的主动吸收。用低钙浴液灌注可重复维拉帕米从肠腔表面刺激结肠水吸收的作用。这表明大鼠结肠顶端膜存在钙通道，这些通道似乎参与基础水转运的调节，且在基础条件下这些钙通道处于部分开放状态。由于维拉帕米既能全身刺激吸收（回肠）又能肠腔内刺激吸收（结肠），钙通道阻滞剂可能具有治疗腹泻性疾病的有用特性。
