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This Article Accepted manuscript (PDF) All Versions of this Article: JOE-09-0199v1 202/3/473    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Ørnsrud, R. Articles by Flik, G. PubMed PubMed Citation Articles by Ørnsrud, R. Articles by Flik, G.

R Ørnsrud, Seafood safety, NIFES, Bergen, Norway
E Lock, Seafood safety, NIFES, Bergen, Norway
C Glover, School of Biological Sciences, University of Canterbury, Christchurch, New Zealand
G Flik, Department of Animal Physiology, Radboud University Nijmegen, Nijmegen, Netherlands

Correspondence: Robin Ørnsrud, Email: robin.ornsrud{at}nifes.no

Vitamins A (VA) and D (VD) are metabolised by vertebrates to bioactive retinoic acid (RA) and calcitriol (CTR). RA and CTR involvement in bone metabolism requires fine-tuned regulation of their synthesis and breakdown. In mammals antagonism of VA and VD is observed, but the mechanism of interaction is unknown. We investigated VA-VD interactions in Atlantic salmon (Salmo salar L.) following intraperitoneal injection of RA and/or CTR. VA metabolites, CTR, calcium, magnesium and phosphorus were determined in plasma. Expression of bone matrix gla protein (mgp), collagen 1 alpha2 chain (col1a2) and alkaline phosphatase (alp) mRNA was quantified to reflect osteogenesis. Branchial epithelial calcium channel mRNA levels (eCac) and intestinal calcium and phosphorus influx were determined to study calcium/phosphorus handling targets of RA and CTR. RA-injection (with or without CTR) decreased plasma CTR-levels 3- to 6-fold. CTR-injection did not affect RA metabolites, but lowered CTR in plasma 3 and 5 days after injection. Lowered plasma CTR correlated with decreased mgp and col1a2 expression in all groups and with decreased alp in CTR-injected fish. RA-treated salmon had enhanced alp expression, irrespective of reduced plasma CTR. Expression of eCac and unidirectional intestinal influx of calcium were stimulated following RA-CTR treatment. Plasma Ca, Mg and P were not affected by any treatment. The results suggest cross-talk of RA with the vitamin D endocrine system in Atlantic salmon. Enhanced calcium flux and osteogenesis (alp transcription) in RA-treated fish and inhibition of mgp expression revealed unprecedented disturbance of calcium physiology in hypervitaminosis A.