In vivo evidence for the intermediary role of 3',5'-cyclic AMP in parathyroid hormone-induced stimulation of 1alpha,25-dihydroxyvitamin D3 synthesis in rats.
Teh stimulatory effect of parathyroid hormone (PTH) on renal 1alpha-hydroxylation of 25-hydroxyvitamin D3 (25-OH-D3) was studied in thyro-parathyroidectomized (TPTX), vitamin D-deficient rats into which bovine PTH, theophylline, cAMP or dibutyryl cAMP (dbcAMP) was constantly infused. The accumulation in plasma of 1alpha,25-dihydroxy-vitamin D3 [1alpha,25-(OH)2-D3], produced from 25-OH-D3, was enhanced by infusion of either cAMP (0.9 MUMOL/H) OR DBCAMP (1 mumol/h) to a level similar to the maximum obtained by PTH (i95--7.5 U/h) infusion. A submaximal dose (1 U/h) of PTH caused a similar extent of stimulation, when infused with theophylline. When either 2 mumol/h of cAMP or 7.5 U/h of bovine PTH was infused starting 18 h after TPTX, the accumulation of 1alpha,25-(OH)2-D3 in plasma was similarly restored withing 6 h to the level found in the sham-operated animals. These results strongly support the concept that cAMP plays an important intermediary role in the stimulation of 1alpha,25-(OH)2-D3 production induced by both exogenous and endogenous PTH.
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000097:blood; D000242:Cyclic AMP / Q000494:pharmacology*; D004100:Dihydroxycholecalciferols / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D006887:Hydroxycholecalciferols / Q000096:biosynthesis* / Q000378:metabolism; D008297:Male; D010280:Parathyroid Glands / Q000502:physiology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D010758:Phosphorus / Q000097:blood; D051381:Rats; D013806:Theophylline / Q000494:pharmacology; D013965:Thyroidectomy; D014808:Vitamin D Deficiency / Q000378:metabolism
D004100:Dihydroxycholecalciferols; D006887:Hydroxycholecalciferols; D010281:Parathyroid Hormone; D010758:Phosphorus; D003994:Bucladesine; D013806:Theophylline; D000242:Cyclic AMP; D002118:Calcium