A role for calmodulin in renal production of 1,25-dihydroxyvitamin D3

Endocrinology
J L TaftR G Larkins

Abstract

The conversion of circulating 25-hydroxyvitamin D3 (25OHD3) to its active metabolite 1,25-dihydroxyvitamin D3 [1,25-(OH)2D3] in the renal tubule mitochondrion by the enzyme 25OHD3-1 alpha-hydroxylase is closely regulated in vivo according to the physiological need for calcium and phosphorus. The mechanism by which this regulation is achieved at the cellular level has not been clarified, although a number of lines of evidence suggest that calcium ions (Ca2+) are involved. This study was designed to determine whether calmodulin, the ubiquitous cell protein that binds and mediates many of the regulatory functions of Ca2+, plays a role in the regulation of renal vitamin D metabolism. The calmodulin antagonists trifluoperazine (TFP), Janssen R24571, and the naphthalene sulfonamides W5 and W7 inhibited conversion of 25OHD3 to 1,25-(OH)2D3 by isolated renal tubules from vitamin D-deficient chicks in a dose-dependent manner (ED50: TFP, 12 mumol/liter; R24571, 10 mumol/liter; W7, 30 mumol/liter; W5, 75 mumol/liter). TFP did not inhibit production of the alternative metabolite 24,25-(OH)2D3 by chick renal tubules. In a similar manner, TFP, W7, and W5 inhibited conversion of 25OHD3 to 1,25-(OH)2D3 by isolated energized chick renal mitocho...Continue Reading

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