Calcifediol antagonizes PTH action on water and phosphate absorption in rabbit pars recta.
Reports of the effects of calcifediol (25-hydroxycholecalciferol) on phosphate excretion, alone or with parathyroid hormone (PTH), or with adenosine 3',5'-cyclic monophosphate (cAMP), have been conflicting. The purpose of this investigation was to examine the effects on fluid and phosphate transport by the rabbit pars recta of calcifediol alone or with PTH. In tubule segments obtained from rabbits fed a normal diet, the addition of 10 or 30 nM calcifediol to the bath did not alter fluid absorption (Jv) or lumen-to-bath phosphate flux (JPil----b). However, pharmacological concentrations did inhibit Jv by 20.9 +/- 5.6% (100 nM, P less than 0.02) and 37.9 +/- 9.4% (1.0 microM, P less than 0.01) and JPil----b by 18.5 +/- 6.6% (100 nM, P less than 0.05) and 40.5 +/- 8.6% (1.0 microM, P less than 0.01). In the presence of 30 nM, 100 nM, or 1.0 microM calcifediol, neither 0.25 nor 1.0 U/ml PTH inhibited JPil----b. A modest decline in Jv did occur with 1.0 U/ml PTH in the presence of 30 nM and 100 nM calcifediol. Unlike calcifediol, when 10 nM calcitriol (1,25-dihydroxycholecalciferol) was present in the bath, 0.2 U/ml PTH significantly depressed Jv and JPil----b. To investigate the mechanism of action of high calcifediol concentration, measurement of the collected minus perfused tubule fluid chloride concentration difference was performed.(ABSTRACT TRUNCATED AT 250 WORDS)
Peraino
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Department of Medicine, Methodist Hospital, Houston, Texas 77030.
Rouse
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Suki
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D000042:Absorption; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D001834:Body Water / Q000378:metabolism*; D002112:Calcifediol / Q000494:pharmacology*; D000242:Cyclic AMP / Q000494:pharmacology; D005260:Female; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010710:Phosphates / Q000378:metabolism*; D011817:Rabbits
D010281:Parathyroid Hormone; D010710:Phosphates; D000242:Cyclic AMP; D002112:Calcifediol