guanylyl-imidodiphosphate and Vitamin-D-Deficiency

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 x 10(-6)M) 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.

Topics: Adenylyl Cyclases; Animals; Calcifediol; Calcitriol; Chickens; Cyclic AMP; Dinoprostone; Guanylyl Imidodiphosphate; Kidney Tubules; Kinetics; Male; Prostaglandins E; Sodium Fluoride; Vitamin D Deficiency