Evidence that adenosine 3',5'-monophosphate mediates hormonal stimulation of prostaglandin production in cultured mouse parietal bones.
The present investigation was undertaken to examine the possible role of cAMP in PTH-stimulated prostaglandin (PG) production in organ cultures of neonatal mouse parietal bones. Cultures were treated with PTH, forskolin, isobutylmethylxanthine (IBMX), and 8-bromo-cAMP (8BrcAMP). We found that similar concentrations of PTH stimulate cAMP formation and increase PG production in this culture system. Forskolin, a direct activator of adenylate cyclase, was also a potent stimulator of cAMP and PG production. The effect was dose dependent, with a maximum at 10(-5) M. The time courses for PTH- and forskolin-stimulated PG production were similar, and there was a close and similar correlation between cAMP production at 15 min and PGE2 production at 6 h for both agents. An increase in PG production was also observed when IBMX, which elevates cAMP levels in cells by inhibiting cAMP phosphodiesterase, or the cAMP analog 8BrcAMP was added to the cultures. In addition, IBMX enhanced the PGE2 responses to PTH, forskolin, and 8BrcAMP. These findings indicate that stimulation of PG production by PTH may be mediated by cAMP.
Division of Endocrinology and Metabolism, School of Medicine, University of Connecticut Health Center, Farmington 06032.
J
J
Klein-Nulend
P N
PN
Bowers
L G
LG
Raisz
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn / Q000378:metabolism; D001842:Bone and Bones / Q000187:drug effects / Q000378:metabolism*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000502:physiology*; D015232:Dinoprostone / Q000096:biosynthesis*; D006854:Hydrocortisone / Q000494:pharmacology; D007700:Kinetics; D051379:Mice; D009924:Organ Culture Techniques; D010281:Parathyroid Hormone / Q000494:pharmacology*
D010281:Parathyroid Hormone; D005576:Colforsin; D015124:8-Bromo Cyclic Adenosine Monophosphate; D000242:Cyclic AMP; D015232:Dinoprostone; D015056:1-Methyl-3-isobutylxanthine; D006854:Hydrocortisone