Plasma Delivery of Retinoic Acid to Tissues in the Rat

All- trans -retinoic acid (RA) activates ligand-dependent transcription factors that regulate retinoid-responsive gene expression. It is assumed that all- trans -RA is formed within cells through in situ oxidation of retinol derived from the circulation. However, the circulation contains low levels...

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Bibliographic Details
Published in:The Journal of biological chemistry 1995-07, Vol.270 (30), p.17850-17857
Main Authors: Kurlandsky, S B, Gamble, M V, Ramakrishnan, R, Blaner, W S
Format: Article
Language:English
Subjects:
Adipocytes - metabolism
Adipose Tissue - metabolism
Animals
Brain - metabolism
Cell Line
Chromatography, High Pressure Liquid
Half-Life
Liver - metabolism
Male
Rats
Rats, Sprague-Dawley
Testis - metabolism
Tissue Distribution
Tretinoin - blood
Tretinoin - pharmacokinetics
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Summary:All- trans -retinoic acid (RA) activates ligand-dependent transcription factors that regulate retinoid-responsive gene expression. It is assumed that all- trans -RA is formed within cells through in situ oxidation of retinol derived from the circulation. However, the circulation contains low levels of all- trans -RA (approximately 0.2-0.7% of that of plasma retinol). Our studies investigated the extent to which plasma all- trans -RA contributes to tissue pools of this retinoid and explored factors responsible for regulating its uptake by tissues and cells. Rats were continuously infused, to steady state, with all- trans -[ 3 H]RA. From measures of specific activities of all- trans -[ 3 H]RA at steady state, we determined that the preponderance of all- trans -RA in brain and liver was derived from the circulation. For six other tissues, approximately 10-30% of the retinoid was derived from the circulation, but pancreas and testis derived very little from the circulating pool. In other studies, we showed that retinoid nutritional status influences clearance of a bolus dose of all- trans -RA and that neither the rate of cellular all- trans -RA uptake nor its intracellular half-life is influenced by cellular lipid levels. Taken together, our data indicate that plasma all- trans -RA contributes to tissue pools of this retinoid and that specific and physiologically responsive cellular processes mediate its uptake.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.270.30.17850