Effect of nocodazole on the water permeability response to vasopressin in rabbit collecting tubules perfused in vitro.

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Abstract
1. The effect of the microtubule‐disruptive agent, nocodazole (methyl [5‐(2‐thienylcarbonyl)‐1H‐benzimidazol‐2‐yl] carbamate), on the water permeability response to vasopressin or the synthetic cyclic AMP analogue, 8‐parachlorophenylthio‐cyclic AMP (8‐CPT‐cAMP), has been investigated in isolated cortical collecting tubules from rabbit kidneys, perfused in vitro. 2. Pre‐treatment with nocodazole, 1‐4 micrograms ml‐1, had no significant effect on basal water permeability, but inhibited the increase in hydraulic conductivity elicited by vasopressin, 50 microU ml‐1, in a dose‐dependent manner. Inhibition of the response to the hormone averaged 65 +/‐ 6% (n = 8, P less than 0.001) at a nocodazole concentration of 4 micrograms ml‐1. 3. Nocodazole, 1‐4 micrograms ml‐1, had no effect on the increase in lumen‐negative potential difference (PD) induced by the hormone. 4. Pre‐treatment with nocodazole, 4 micrograms ml‐1, inhibited the development of the water permeability response to 8‐CPT‐cAMP, 1.8 x 10(‐5) M, by 45 +/‐ 7% (n = 7, P less than 0.001). 5. When collecting tubules were exposed to nocodazole, 4 micrograms ml‐1, after the hydrosmotic response to vasopressin had been fully established, the drug had no inhibitory effect on the maintenance of a high water permeability. 6. The results are consistent with the view that cytoplasmic microtubules play a role in the initiation of the water permeability response to vasopressin in the mammalian cortical collecting tubule at a cellular site beyond the generation of cyclic AMP.