YM175, a new bisphosphonate, increases serum 1,25-dihydroxyvitamin D in rats via stimulating renal 1-hydroxylase activity.
Effect of YM175, a new bisphosphonate, on vitamin D metabolism was studied in rats. When animals were treated with the compound, serum 1,25-dihydroxyvitamin D increased in a dose dependent manner. The effect was also detected in thyroparathyroidectomized animals. The effect appears to be due to the stimulation of renal production of the hormone, since renal 1-hydroxylase was also elevated in these animals. However, when kidneys were incubated with YM175 and then renal 1-hydroxylase activity was examined, the enzyme activity was not different from that of non-treated control kidney. We conclude therefore that YM175 indirectly stimulates renal 25-hydroxyvitamin D-1-hydroxylase by increasing circulating parathyroid hormone via an unknown mechanism independent of parathyroid hormone. This is the first direct demonstration of increase in the renal production of 1,25-dihydroxyvitamin D resulting from bisphosphonate treatment.
Nagao
Y
Y
Medicinal Research Laboratories, Yamanouchi Pharmaceutical Co., Ltd., Ibaraki, Japan.
Ishitobi
Y
Y
Kinoshita
H
H
Fukushima
S
S
Kawashima
H
H
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism*; D000818:Animals; D002117:Calcitriol / Q000097:blood*; D002118:Calcium / Q000097:blood; D004164:Diphosphonates / Q000494:pharmacology*; D007668:Kidney / Q000201:enzymology*; D008297:Male; D008928:Mitochondria / Q000201:enzymology; D016105:Parathyroidectomy; D010710:Phosphates / Q000097:blood; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013965:Thyroidectomy
D004164:Diphosphonates; D010710:Phosphates; C071542:cimadronate; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol; D002118:Calcium