Effects of colchicine and vinblastine on the cellular action of vasopressin in mammalian kidney. A possible role of microtubules.
Effects of colchicine and vinblastine on the cellular action of vasopressin in mammalian kidney. A possible role of microtubules.
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秋水仙碱和长春花碱对哺乳动物肾脏中加压素细胞作用的影响。
DOI：
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发表时间：
1974
影响因子：
15.9
通讯作者：
L. D. Barnes
中科院分区：
文献类型：
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作者：
T. Dousa;L. D. Barnes
为了评估微管在加压素对哺乳动物肾脏的细胞作用中的可能作用，在体内和体外研究了微管破坏剂的作用。在大鼠中进行了体内研究，通过饮用5%葡萄糖诱导轻度至中度水利尿。微管破坏生物碱，秋水仙碱（0.1毫克/天）或长春碱（0.08毫克/天），腹腔注射，不改变水和溶质排泄本身，但阻止或显着抑制抗利尿反应（增加尿渗透压和减少尿流量）外源性加压素。总溶质排泄不受这两种生物碱的影响，钠、钾或肌酐排泄无实质性变化。Lumicolchicine是秋水仙碱的衍生物，不与微管相互作用，不改变对外源性加压素的抗利尿反应。在离体条件下，10（-5）-10（-4）M秋水仙碱或长春碱对肾髓质质膜腺苷酸环化酶、肾髓质胞液cAMP磷酸二酯酶和蛋白激酶活性无影响。对肾髓质中微管蛋白（评估为[（3）H]秋水仙素结合蛋白）的亚细胞分布的研究表明，该蛋白主要包含在细胞质中。颗粒部分，包括质膜，仅含有微量（小于6%）的秋水仙素结合活性。结果表明，在远端肾单位的细胞中的细胞质微管的完整性所需的加压素的抗利尿作用，可能在该网站的远端环AMP生成在哺乳动物肾脏。
To evaluate the possible role of microtubules in the cellular action of vasopressin on the mammalian kidney, the effects of microtubule-disrupting agents were studied in vivo and in vitro. In vivo studies were done in rats in mild to moderate water diuresis induced by drinking 5% glucose. Microtubule-disrupting alkaloids, colchicine (0.1 mg/day) or vinblastine (0.08 mg/day), given intraperitoneally, did not change water and solute excretion itself, but blocked or markedly inhibited the antidiuretic response (increase in urine osmolality and decrease in urine flow) to exogenous vasopressin. Total solute excretion was unaffected by these two alkaloids and there were no substantial changes in excretion of sodium, potassium, or creatinine. Lumicolchicine, a derivative of colchicine that does not interact with microtubules, did not alter the antidiuretic response to exogenous vasopressin. Activities of adenylate cyclase in the renal medullary plasma membrane, and cyclic AMP phosphodiesterase and protein kinase in renal medullary cytosol, were not influenced by 10(-5)-10(-4) M colchicine or vinblastine in vitro. Studies on the subcellular distribution of microtubular protein (assessed as [(3)H]colchicine-binding protein) in renal medulla shows that this protein is contained predominantly in the cytosol. Particulate fractions, including plasma membrane, contain only a minute amount (less than 6%) of the colchicine-binding activity. The results suggest that the integrity of cytoplasmic microtubules in cells of the distal nephron is required for the antidiuretic action of vasopressin, probably in the sites distal to cyclic AMP generation in the mammalian kidney.