Biphasic action of prostaglandin E2 on conversion of 25-hydroxyvitamin D3 to 1,25-dihydroxyvitamin D3 in chick renal tubules

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Abstract

The effect of PGE2 on the conversion of 25-hydroxyvitamin D3 (25 OH D3) to 1,25-dihydroxyvitamin D3 (1,25- (OH) 2D3) by isolated renal tubules from vitamin D deficient chicks was studied under a variety of experimental conditions. In the absence of added vitamin D metabolites, PGE2 (2 × 10−6M) caused an immediate inhibition of formation of 1,25-(OH) 2D3, followed by a delayed stimulation, apparent after 15 h exposure to PGE2. Pretreatment of the tubules with 1,25-(OH) 2D3 prevented the immediate inhibitory action of PGE2, and allowed the stimulation to be apparent after 4 h exposure to PGE2. The cyclic nucleotide phosphodiesterase inhibitor 3-isobutyl-1-methyl xanthine (IBMX) significantly stimulated the formation of 1,25-(OH) 2D3. PGE2 significantly inhibited 1,25-(OH) 2D3 formation in tubules which had been stimulated by IBMX. PGE2 stimulated the adenylate cyclase activity in a crude particulate fraction from the chick kidney, and raised cyclic adenosine 3′, 5′-monophosphate (cyclic AMP) levels in the renal tubules.

It is concluded that PGE2 can either stimulate or inhibit 1,25-(OH) 2D3 formation in chick renal tubules. The stimulatory effect may be partly due to elevation of cyclic AMP. The mechanism of the inhibitory effect requires further investigation.

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