Inhibition by prostaglandin E2 of renal effects of calcitonin in rats.
To investigate the possible role of prostaglandin E2 (PGE2) in modulating the actions of PTH and calcitonin (CT) in the kidney, the effects of PGE2 were examined on the in vivo conversion of [3H]25-hydroxyvitamin D3 to [3H]1,25-dihydroxyvitamin D3 ([3H]1,25-(OH)2D3) in vitamin D-deficient thyroparathyroidectomized (T-PTX) rats and on the urinary excretion of phosphate (Pi) in vitamin D-replete T-PTX rats in the presence of either PTH or CT. Plasma accumulation of [3H] 1,25-(OH)2D3 increased from 12.2 +/- 0.6 pmol/100 ml in controls to 19.5 +/- 1.1 (P less than 0.01) by 20 micrograms/h PGE2 to 29.8 +/- 1.8 (P less than 0.001) by 7.5 U/h PTH, and to 23.3 +/- 0.7 (P less than 0.01) by 500 mU/h CT. Administration of PGE2 inhibited CT-stimulated accumulation of 1,25-(OH)2D3 to levels not different from those by PGE2 alone (17.8 +/- 1.0 pmol/100 ml). In contrast, PGE2 had no effect on PTH-stimulated 1,25-(OH)2D3 accumulation. PTH and CT caused an increase in urinary Pi excretion and a decrease in plasma Pi levels. PGE2 abolished the effects of CT, but not of PTH, on both urinary Pi excretion and plasma Pi levels. Administration of PGE2 alone caused no significant changes in plasma Pi levels and only minimal increase in urinary Pi excretion. PGE2 did not suppress urinary cAMP excretion stimulated by CT. These results demonstrate that PGE2 specifically suppresses the effects of CT to stimulate synthesis of [3H]1,25-(OH)2D3 from [3H]25-hydroxyvitamin D3 and to inhibit tubular reabsorption of Pi without affecting urinary cAMP excretion. Since CT appears to stimulate 1 alpha-hydroxylase and inhibit Pi reabsorption in proximal tubules, nephron segments devoid of CT-sensitive adenylate cyclase, these data suggest that PGE2 modulates the actions of CT, but not of PTH, on proximal tubular functions.
D000818:Animals; D002112:Calcifediol / Q000097:blood; D002116:Calcitonin / Q000037:antagonists & inhibitors*; D002117:Calcitriol / Q000378:metabolism; D015232:Dinoprostone; D007668:Kidney / Q000187:drug effects*; D008297:Male; D010280:Parathyroid Glands / Q000187:drug effects; D010710:Phosphates / Q000652:urine; D011458:Prostaglandins E / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014808:Vitamin D Deficiency / Q000097:blood; D014886:Weaning
D010710:Phosphates; D011458:Prostaglandins E; D002116:Calcitonin; D002117:Calcitriol; D015232:Dinoprostone; D002112:Calcifediol