Vasopressin: Possible Role of Microtubules and Microfilaments in Its Action

Abstract

Colchicine, vinblastine, podophyllotoxin, and cytochalasin B inhibit the action of vasopressin and cyclic adenosine monophosphate on osmotic water movement across the toad bladder. The findings suggest that microtubules, and possibly microfilaments, play a role in the action of vasopressin, perhaps through involvement in the mechanism of release of secretory material from the bladder epithelial cells.

Effects of Colchicine and Vinblastine on the Cellular Action of Vasopressin in Mammalian Kidney A POSSIBLE ROLE OF MICROTUBULES

“…The view that colchicine and vinblastine blocked the effect of exogenous vasopressin by interfering with its cellular-action on the distal nephron finds further support in reported observations on the toad bladder (6). In that system the tested alkaloids blocked the effect of (10).…”

“…Since no changes in UVoum occurred, solute washout due to osmotic diuresis is not likely. UVNa did not increase (with the exception of a slight transitory increase on day 4 in the presence of colchicine) and this indicates that no major depression of sodium reabsorption (such as occurs after administration of 0.84±0.07 (7) 0.54±0.09 (7) 2.2540.206 (7) Preincubated with colchicine 0.21±0.02 (6) 0.78±0.03 (6) 0.46±0.04 (6) 2.16±0.65 (6) Preincubated with vinblastine 0.2140.02 (6) 0.79±0.07 (6) 0.44±0.07 (6) 2.2140.22 (6) Preincubation conditions as in Table IV. Activities of enzymes incubated with alkaloids were not significantly different (P > 0.05) from controls when evaluated by t test for paired observations.…”

“…Colchicine-binding protein in renal medullary cytosol showed some characteristic properties described for analogous protein from brain (19): the colchicine-binding activity was labile after prolonged incubation of 00C or after short incubation at 60'C, and (3) 4.98±0.33 (3) 4.86±0.12 (3) 38.4±0.56 (3) 42.434±2.26 (3) 39.1 1 ±2.35 (3) Cyclic AMP phosphodiesterase after preincubationj with colchicine or vinblastine nmol/min per mg protein* control 1.61±0.11 (6) Preincubated with colchicine 1.62±i0.11 (6) Preincubated with vinblastine 1.58±0.16 (6) * Mean±SE; number of experiments in parentheses. colchicine-binding protein was completely precipitated from the cytosol by incubation with vinblastine (Table VI).…”

“…Still hypothetical is the idea that cyclic AMP acts on the lumenal plasma membrane through its influence on protein phosphorylation (3)(4)(5). Taylor, Mamelak, Raven, and Maffly (6) found that some drugs known to disrupt the structure of microtubules partially inhibit the increase in water permeability in response to vasopressin and exogenous cyclic AMP in isolated toad urinary bladders. The stimulatory effect of vasopressin and cyclic AMP on active sodium transport in the same tissue was not influenced by these drugs.…”

Modulation of the hepatic α1‐adrenoceptor responsiveness by colchicine: dissociation of free cytosolic Ca2+‐dependent and independent responses

“…substrate for pertussis or cholera toxin catalysed ADP-ribosylation (Amir-Zaltsman et al, 1982;Wang et al, 1990) and seems to control cellular Ca2" fluxes (Lim et al, 1985). Based on these and other (Taylor et al, 1973;Omann et al, 1987) observations that suggest the implication of the cytoskeleton in the signal transduction mechanism of plasma membrane receptors, we found it interesting to determine the role of the cytoskeleton on the hepatic al-adrenoceptor signalling pathway. For this purpose, we used the microtubular depolymerizing agent colchicine (Wilson et al, 1974) and determined its effect on the al-adrenoceptor-mediated responses of isolated perfused livers.…”