cyclic-gmp and Vitamin-D-Deficiency

The development of experimental vitamin D deficiency in rats was accompanied by changes in cyclic nucleotides metabolism in the cortical part of kidneys, namely the increase in cyclic AMP synthesis and the decrease in cyclic GMP. The above changes appear in combination with marked deviations in calcium/phosphorus metabolism.

Topics: Animals; Cyclic AMP; Cyclic GMP; Female; Kidney Cortex; Male; Rats; Vitamin D Deficiency

The conversion of 25-hydroxyvitamin D3 (25 OH D3) to 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3), 24,25-dihydroxyvitamin D3 (24,25-(OH)2D3) and 1,24,25-trihydroxyvitamin D3 (1.24,25-(OH)3D3) was studied in renal tubules prepared from chicks raised on a vitamin D deficient diet with or without vitamin D supplementation. As described previously, in tubules from vitamin D deficient chicks, cyclic AMP caused an increase in the net accumulation of 1,25-(OH)2D3, the major metabolite formed under these circumstances. This stimulation was shown to be due to an increased maximum velocity of the hydroxylation reaction. There was also a significant inhibition of the net accumulation of 24,25-(OH)2D3. Cyclic GMP caused a significant inhibition of 1,25-(OH)2D3 formation and stimulation of the net accumulation of 24,25-(OH)2D3. In chicks supplemented with high doses of vitamin D, 24,25-(OH)2D3 was the major metabolite of 25 OH D3 detected and 1-hydroxylase activity was negligible. Under these circumstances, neither cyclic AMP nor cyclic GMP affected net accumulation of 24,25(OH)2D3. This suggested that the apparent effect of the nucleotides on formation of 24,25-(OH)2D3 may have been due to further metabolism of 24,25-(OH)2D3 when 1-hydroxylase activity was high. It is concluded that cyclic AMp and cyclic GMP have reciprocal effects on renal 25 OH D3-1-hydroxylase activity, and both should be considered potential intracellular regulators of 25 OH D3 metabolism.

Topics: 24,25-Dihydroxyvitamin D 3; Animals; Calcifediol; Calcitriol; Chickens; Cyclic AMP; Cyclic GMP; Dihydroxycholecalciferols; Hydroxycholecalciferols; Kidney Tubules; Male; Vitamin D Deficiency

Topics: Animals; Calcitriol; Calcium; Chickens; Cyclic GMP; Dihydroxycholecalciferols; Duodenum; Hydroxycholecalciferols; Intestinal Mucosa; Male; Vitamin D Deficiency

Topics: Animals; Bone and Bones; Calcium; Calcium, Dietary; Cholecalciferol; Cyclic AMP; Cyclic GMP; DNA; Male; Nucleotides, Cyclic; Rats; Skull; Vitamin D Deficiency

A single 270 ng dose of 1alpha,25-(OH2D3 rpoduced elevations in cyclic AMP content and adenylate cyclase activity in duodenal mucosa from previously vitamin D-deficient rats. No changes in jejunal or ileal cyclic AMP levels or duodenal cyclic GMP levels were observed. Since 1alpha,25-(OH)2D3 increased both baseline and NaF-stimulated adenylate cyclase activity, it is possible that the vitamin leads to enhanced enzyme synthesis. While parallel changes in duodenal cyclic AMP levels and active calcium absorption in response to 1alpha,25-(OH)2D3 were observed at 6,12,24 and 48 hr after treatment, increases in calcium absorption were observed at 3 hr in duodenum and at 48 hr in ileum in the absence of changes in cyclic AMP levels. Further studies will be required to determine whether or not the changes in duodenal cyclic AMP levels are direct or indirect effects of 1alpha,25-(OH)2D3 administration, and to determine the role, if any, of this nucleotide in the hormones' effect on intestinal calcium absorption.

Topics: Adenylyl Cyclases; Animals; Calcium; Cyclic AMP; Cyclic GMP; Dihydroxycholecalciferols; Duodenum; Hydroxycholecalciferols; Ileum; Intestinal Mucosa; Jejunum; Male; Rats; Vitamin D Deficiency