Colchicine does not interfere with the antiphosphaturic effect of 25(OH) vitamin D3 in the rat

Abstract

The effect of colchicine pretreatment on the antiphosphaturic action of 25(OH)vitamin D3 (25[OH]D3) was examined in parathyroidectomized (PTX), parathyroid-hormone (PTH)-infused rats by acute clearance studies. The following groups were studied: group 1, colchicine-pretreated PTX rats; group 2, colchicine-pretreated PTX rats receiving PTH infusion; group 3, colchicine-pretreated PTH-infused PTX rats receiving intravenous 25(OH)D3 with pretreated PTH-infused PTX rats serving as controls. The effect of 25(OH)D3 on PTH-activated renal adenylate cyclase [AC] from colchicine-pretreated rats was studied in vitro. In group 1, fractional excretion of phosphate (Cp/CIn) after colchicine was 0.102 +/- 0.011 vs. 0.029 +/- 0.005 in controls (p less than 0.001). In group 2, PTH increased Cp/CIn from 0.074 +/- 0.026 to 0.184 +/- 0.028 (p less than 0.05) in colchicine-pretreated animals and from 0.018 +/- 0.006 to 0.213 +/- 0.034 in controls (p less than 0.0025). In group 3, 25(OH)D3 decreased Cp/CIn from 0.344 +/- 0.022 to 0.235 +/- 0.026 (p less than 0.005) and UcAMP from 103.7 +/- 12.4 to 69.0 +/- 9.6 (p less than 0.025). In vitro PTH activation of AC was blunted in colchicine-pretreated rats; however, the response to 25(OH)D3 was intact. Histological changes compatible with microtubule disruption were found in proximal tubules of kidneys from colchicine-pretreated rats. These results show that colchicine alters the response to PTH but it does not affect the antiphosphaturic action of 25(OH)D3, suggesting that this action is not mediated via cytoplasmic microtubules.