Sodium nitroprusside increases cyclic GMP in fetal rat bone cells and inhibits resorption of fetal rat limb bones.
To elucidate the role of cGMP in bone resorption, the nucleotide was measured in bone and bone cells in response to several agents including stimulators of bone resorption. In other experiments, sodium nitroprusside (SNP), which elevates bone cGMP, was tested for effects on resorption. In cells from 20-day fetal rat calvaria, cGMP was 52.4 +/- 8.4 fmol/10(6) cells; cAMP was 5.3 +/- 0.3 pmol/10(6) cells. SNP, 0.1 mM, in the presence of IBMX, increased cGMP 74% with no significant effect on cAMP. Parathyroid hormone (PTH), 0.5 microM, did not significantly affect cGMP, but increased cAMP 711%. Calcitriol did not affect either nucleotide. In bone resorption studies, 0.1 mM SNP inhibited the effects of PTH and calcitriol. Lower concentrations of SNP (0.001, 0.01 mM) had no effects on hormone-stimulated resorption. Unstimulated control bones were not affected by 1 nM-1 mM SNP. The results suggest that elevated cGMP could result in inhibition of bone resorption.
Stern
P H
PH
Department of Pharmacology, Northwestern University Medical School, Chicago, IL 60611.
Diamond
J
J
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001862:Bone Resorption / Q000378:metabolism* / Q000517:prevention & control; D001842:Bone and Bones / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism; D002117:Calcitriol / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D005121:Extremities; D005333:Fetus; D009599:Nitroprusside / Q000494:pharmacology*; D010281:Parathyroid Hormone / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats
D010281:Parathyroid Hormone; D009599:Nitroprusside; D000242:Cyclic AMP; D002117:Calcitriol; D006152:Cyclic GMP; D015056:1-Methyl-3-isobutylxanthine