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M M Pechet

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Demonstration of the rapid action of pure crystalline 1 alpha-hydroxy vitamin D3 and 1 alpha,25-dihydroxy vitamin D3 on intestinal calcium uptake.

The biological effects of crystalline 1alpha-hydroxyvitamin D3 and crystalline 1alpha,25-dihydroxyvitamin D3 have been compared on the intestinal uptake of calcium-45 by everted duodenal gut sacs from rachitic rats. Peak calcium-45 uptake was observed 1 hr after intravenous administration and both crystalline vitamin D2 analogs were of comparable potency. The rapid onset of calcium-45 uptake and the rapid attainment of maximal calcium-45 transport suggests a direct effect of these crystalline analogs on the mucosal membranes of the intestinal cell.

Animals

Biological activity of 1alpha-hydroxycholecalciferol, a synthetic analog of the hormonal form of vitamin D3.

1,25-Dihydroxycholecalciferol, the apparent active hormonal form of cholecalciferol (vitamin D(2)), is formed from cholecalciferol by specific and sequential hydroxylations of the sterol at carbons 25 and 1. Recently, 1alpha-hydroxycholecalciferol was synthesized and we report on its biological activity in rachitic chicks. 1alpha-Hydroxycholecalciferol is identical in potency to 1,25-dihydroxycholecalciferol in stimulation of intestinal calcium absorption; either sterol elicits a near maximal effect at a dose of 0.3-0.6 nmol. The time-course of action of 1alpha-hydroxycholecalciferol also parallels that of the active metabolite 1,25-dihydroxycholecalciferol with a maximal increase in calcium transport occurring 5-10 hr after administration of sterol to vitamin D-deficient chicks. 6.5 nmol of 1alpha-hydroxycholecalciferol causes a doubling in calcium absorption in only 2-3 hr, which is the most rapid physiologic response yet detected for a vitamin D-sterol. 1alpha-Hydroxycholecalciferol is active also in enhancing bone calcium resorption and, like 1,25-dihydroxycholecalciferol, is at least 10 times as active as cholecalciferol in mobilizing bone calcium and raising plasma calcium concentration. It is concluded that 1alpha-hydroxycholecalciferol represents a synthetic analog of 1,25-dihydroxycholecalciferol that can be used both to study the mechanism of action of this hormone and as a therapeutic agent in the treatment of patients with certain metabolic bone diseases.

Animals

Calcitonin.

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Animals