AJP - Gastrointestinal and Liver Physiology, Vol 248, Issue 6 633-G638, Copyright © 1985 by American Physiological Society
Intestinal metabolism and portal venous transport of 1,25(OH)2D3, 25(OH)D3, and vitamin D3 in the rat
G. B. McDonald, K. H. Lau, A. L. Schy, J. E. Wergedal and D. J. Baylink
We compared the intestinal absorption of three vitamin D3 sterols and
tested the hypothesis that the intestine hydroxylates absorbed vitamin D
and transports polar metabolites in portal venous blood. Micellar solutions
containing 50 nmol of a radiolabeled vitamin D3 sterol
(1,25-dihydroxyvitamin D3, 25-hydroxyvitamin D3, or vitamin D3) were placed
in closed jejunal segments of rats prepared with lymphatic and mesenteric
venous fistulas. Venous blood loss was replaced by infusion of donor rat
blood into the saphenous vein. After 1-2 h the rats were killed, and
intestinal homogenates, mesenteric blood, and lymph were analyzed. The
average rate of absorption of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] was
two- and fivefold higher than that of 25-hydroxyvitamin D3 [25(OH)D3] and
vitamin D3 (D3), respectively. Transport of hydroxylated vitamin D sterols
was primarily via the venous route; the average rate of venous transport of
1,25(OH)2D3 was 18.3 X 10(2) nmol X min-1 X g-1 compared with 8.8 X 10(2)
for 25(OH)D3 and 0.13 X 10(2) for D3. High-performance liquid
chromatography of intestinal and plasma extracts revealed that there was
25-hydroxylation of absorbed D3, 24- and putative 1-hydroxylation of
absorbed 25(OH)D3, and prompt portal venous transport of all hydroxylated
metabolites. When 1,25(OH)2D3 was infused into the lumen, the composition
of radiolabeled sterols found in intestinal homogenates and mesenteric
venous plasma was virtually identical to that of the infusate. These
studies provide in vivo evidence for the intestinal metabolism of
pharmacological quantities of absorbed vitamin D3 sterols and the prompt
portal venous transport of more polar metabolites.
