Intestinal calcium-binding protein (CaBP) and bone calcium mobilization in response to 25R,26 and 25S,26-dihydroxycholecalciferol in intact and nephrectomized rats.
Since intestinal calcium-binding protein (CaBP) can be regarded as an expression of the hormone-like action of 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3) on the duodenal enterocyte we have investigated the potential biological activity of 25R and 25S,26-(OH)2D3 (two recently synthesized epimers of vitamin D3 metabolite) to promote intestinal CaBP production as compared to bone calcium mobilization in vitamin D and calcium-deficient rats. In our assay steroids exhibited a 72 hour calcemic response. Our results show a linear relationship between CaBP synthesis and the logarithm of the dose (130-2080 pmol dose range) of either 25R or 25S epimer. The CaBP response was comparable for both epimers. Similarly bone calcium mobilization response was dose related as a linear function of the logarithm of the administered dose. Again, calcemic response was comparable for both epimers. In our model these two epimers were about as active on intestine to increase CaBP amount as on bone to elevate serum calcium level. Bilateral nephrectomy abolished CaBP response to a large dose (1040 pmol) of either 25R or 25S epimer but did not abolish it to a 130 pmol dose of 1alpha,25-(OH)2D3.
D000818:Animals; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000097:blood / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D004100:Dihydroxycholecalciferols / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006887:Hydroxycholecalciferols / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D008297:Male; D009392:Nephrectomy; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013997:Time Factors
D002352:Carrier Proteins; D004100:Dihydroxycholecalciferols; D006887:Hydroxycholecalciferols; D002118:Calcium