Baron D A, Burch R M, Halushka P V, Spicer S S
Am J Physiol. 1985 Oct;249(4 Pt 2):F464-9. doi: 10.1152/ajprenal.1985.249.4.F464.
Colchicine inhibits vasopressin-induced osmotic water flow across isolated toad urinary bladder. Concomitantly, colchicine has been shown to reduce the relative cytoplasmic volume fraction of microtubules in the apical granular cells of this epithelium that have been shown previously to mediate the hydroosmotic effect of vasopressin. Therefore, an intact cytoskeleton has been postulated to be a requirement for a full response to vasopressin. Since it has been demonstrated recently that cyclooxygenase inhibitors (meclofenamic acid) abrogate the inhibition by colchicine of vasopressin-stimulated water flow, we tested by stereological criteria the hypothesis that colchicine in the presence of meclofenamic acid does not prevent the polymerization of tubulin. Our results show that the relative cytoplasmic volume fraction of microtubules was reduced 75% by colchicine in the presence or absence of meclofenamic acid. An alternative explanation of the inhibitory action of colchicine is its ability in the toad urinary bladder to enhance the endogenous synthesis of and sensitivity to prostaglandin E, a potent negative modulator of vasopressin-stimulated water flow. An intact microtubular component of the cytoskeleton does not appear to be required for a maximal response to a physiological dose of vasopressin.
秋水仙碱可抑制血管加压素诱导的水分通过离体蟾蜍膀胱的渗透流动。同时，秋水仙碱已被证明可降低该上皮顶端颗粒细胞中微管的相对细胞质体积分数，而这些细胞先前已被证明可介导血管加压素的水渗透效应。因此，完整的细胞骨架被认为是对血管加压素产生充分反应的必要条件。由于最近已证明环氧合酶抑制剂（甲氯芬那酸）可消除秋水仙碱对血管加压素刺激的水流的抑制作用，我们通过体视学标准检验了以下假设：在甲氯芬那酸存在的情况下，秋水仙碱不会阻止微管蛋白的聚合。我们的结果表明，无论是否存在甲氯芬那酸，秋水仙碱均可使微管的相对细胞质体积分数降低75%。秋水仙碱抑制作用的另一种解释是，它在蟾蜍膀胱中能够增强前列腺素E的内源性合成及对其的敏感性，而前列腺素E是血管加压素刺激水流的一种强效负调节剂。对于生理剂量的血管加压素产生最大反应而言，完整的细胞骨架微管成分似乎并非必需。
