Effect of 22-oxa-calcitriol on calcium metabolism in rats with severe secondary hyperparathyroidism.
The purpose of the present study was to examine the effect of a two day and a five day administration of 22-oxa-calcitriol (OCT) on calcium metabolism in rats with advanced chronic renal failure and severe secondary hyperparathyroidism. A first series of 27 uremic rats received either placebo, OCT or calcitriol (0.3 microgram i.p./rat) 48 and 24 hours before sacrifice. A second series of 18 uremic rats received either placebo, OCT (0.3 microgram i.p./rat) or calcitriol (0.05 microgram i.p./rat) for five days. We found that after 48 hours (series 1) both calcitriol and OCT increased blood ionized calcium (Ca2+) as compared to vehicle (1.23 +/- 0.04 and 1.10 +/- 0.02 mM, P < 0.01 and P < 0.05, respectively vs. control, 1.02 +/- 0.03 mM). Duodenal Ca transport (S/M) using the everted gut sac technique was not stimulated by OCT, even though it increased from 2.8 +/- 0.4 to 7.0 +/- 0.6 (P < 0.01) with calcitriol. In contrast, duodenal calbindin-D9k mRNA expression and protein content increased to a similar extent with OCT and calcitriol. Calcitriol was more potent in reducing plasma iPTH1-34 levels than OCT: 344 +/- 75 pg/ml (calcitriol) versus 632 +/- 46 pg/ml (OCT) compared with 897 +/- 74 pg/ml (control), P < 0.01. In the second series of rats, the injection of OCT (0.3 microgram i.p./rat) over five days was less effective than the lower dose of calcitriol (0.05 microgram i.p./rat) in reducing circulating iPTH: 110 +/- 26 (calcitriol) and 281 +/- 64 (OCT) versus 624 +/- 135 pg/ml (control), P < 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)
Kubrusly
M
M
INSERM Unité 90, Hôpital Necker, Paris, France.
Gagné
E R
ER
Ureña
P
P
Hanrotel
C
C
Chabanis
S
S
Lacour
B
B
Drüeke
T B
TB
D000818:Animals; D064026:Calbindins; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000494:pharmacology; D002118:Calcium / Q000097:blood / Q000378:metabolism*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004386:Duodenum / Q000378:metabolism; D006962:Hyperparathyroidism, Secondary / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D017136:Ion Transport; D008297:Male; D010281:Parathyroid Hormone / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D064030:S100 Calcium Binding Protein G / Q000378:metabolism; D019379:Teriparatide; D014511:Uremia / Q000150:complications
D064026:Calbindins; D010281:Parathyroid Hormone; D010446:Peptide Fragments; D012333:RNA, Messenger; D064030:S100 Calcium Binding Protein G; C576508:S100g protein, rat; D019379:Teriparatide; D002117:Calcitriol; C051883:maxacalcitol; D002118:Calcium