Effects of colchicine and vinblastine on the cellular action of vasopressin in mammalian kidney. A possible role of microtubules.
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.
D000262:Adenylyl Cyclases / Q000494:pharmacology; D000818:Animals; D003078:Colchicine / Q000494:pharmacology*; D003404:Creatinine / Q000652:urine; D000242:Cyclic AMP / Q000096:biosynthesis / Q000378:metabolism / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D007679:Kidney Medulla / Q000201:enzymology; D008870:Microtubules / Q000187:drug effects / Q000201:enzymology / Q000502:physiology; D009994:Osmolar Concentration; D010727:Phosphoric Diester Hydrolases / Q000494:pharmacology; D010761:Phosphorus Radioisotopes; D011188:Potassium / Q000652:urine; D011494:Protein Kinases / Q000494:pharmacology; D051381:Rats; D012964:Sodium / Q000652:urine; D014316:Tritium; D014667:Vasopressins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014747:Vinblastine / Q000494:pharmacology*; D014882:Water-Electrolyte Balance / Q000187:drug effects*
D010761:Phosphorus Radioisotopes; D014316:Tritium; D014667:Vasopressins; D014747:Vinblastine; D012964:Sodium; D003404:Creatinine; D000242:Cyclic AMP; D011494:Protein Kinases; D010727:Phosphoric Diester Hydrolases; D000262:Adenylyl Cyclases; D011188:Potassium; D003078:Colchicine