Renal parathyroid hormone-dependent adenylate cyclase in vitamin D-deficient rats. Inhibition by hydroxylated vitamin D3 metabolites.
The adenylate cyclase activation by bovine synthetic parathyroid hormone (bPTH) (1-34) was studied in vitro in kidney plasma membranes from D-deficient (D-Mb)  or normal (D+Mb) rats. In D-Mb, the apparent affinity of parathyroid hormone (PTH) for membranes (170 +/- 30 nM) was significantly higher than that measured in D+Mb (55 +/- 5 nM). The maximum velocity of the PTH-stimulated adenylate cyclase was significantly higher in D+Mb than in D-Mb (163.0 +/- 13.7 and 93.4 +/- 6.7 pmol of cAMP/mg of protein/min, respectively). The action of vitamin D metabolites on the adenylate cyclase stimulation by PTH was then studied in vitro in D-Mb and D+Mb. In D-Mb, 25-hydroxyvitamin D3, 24,25-, and 1, 25-dihydroxyvitamin D3 significantly inhibited cAMP production in the presence of 0.87 microM of bPTH. Vitamin D3 had no effect. Maximal inhibition (86%) was observed for 1,25-dihydroxyvitamin D3. 1,25-Dihydroxyvitamin D3 decreased the maximum velocity of PTH-stimulated adenylate cyclase but did not modify the bPTH apparent affinity for D-Mb. The vitamin D3 metabolites tested did not modify the cyclase stimulation by isoproterenol, sodium fluoride, or 5'-guanylylimidodiphosphate. The presence of 1,25-dihydroxyvitamin D3 or 25-hydroxyvitamin D3 did not increase the (Na-K)-ATPase or the phosphodiesterase activities. In the presence of 1,25-dihydroxyvitamin D3 and bPTH, the apparent affinity of ATP for the catalytic moiety was not modified. The maximum velocity was decreased. These results suggest an in vitro interaction between hydroxylated vitamin D metabolites and kidney membranes PTH receptor.
D015650:24,25-Dihydroxyvitamin D 3; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002117:Calcitriol; D002462:Cell Membrane / Q000201:enzymology; D002762:Cholecalciferol / Q000494:pharmacology; D004100:Dihydroxycholecalciferols / Q000494:pharmacology; D007668:Kidney / Q000201:enzymology*; D007700:Kinetics; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology*; D051381:Rats; D014808:Vitamin D Deficiency / Q000201:enzymology*
D004100:Dihydroxycholecalciferols; D010281:Parathyroid Hormone; D002762:Cholecalciferol; D015650:24,25-Dihydroxyvitamin D 3; D000262:Adenylyl Cyclases; D002117:Calcitriol