Stimulation of CFU-f formation by prostaglandin E2 is mediated in part by its degradation product, prostaglandin A2.
Prostaglandins (PG) of the E series are known to rapidly undergo non-enzymatic dehydration in culture medium containing serum albumin to produce the cyclopentenone PGs of the A series. We investigated the actions of PGA1 and A2 in the in vitro calcifying fibroblastic-colony forming unit assay which can partially mimic the in vivo anabolic effects of PGE2. It was found that PGA1 and A2 both stimulated colony formation in a dose-dependent manner with a maximum at 10(-6) M and to a similar degree to PGE2. In contrast to PGE2, PGA1 and PGA2 both caused an inhibition of cAMP accumulation. Furthermore, the addition of protein kinase A inhibitors, H8 and H89, had no significant effect on the stimulation of colony number by PGE2. These data suggest that (a) the bone anabolic effects of PGE1 and E2 are, in part at least, mediated by their dehydration products PGA1 and A2 and (b) that they are mediated via pathways not necessarily involving the cAMP/protein kinase A cascade.
Still
K
K
Institute of Child Health, Children's Hospital, Western Bank, Sheffield, UK.
Scutt
A
A
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D015232:Dinoprostone / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005347:Fibroblasts / Q000166:cytology* / Q000187:drug effects; D006868:Hydrolysis; D008297:Male; D011454:Prostaglandins A / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar
D004791:Enzyme Inhibitors; D011454:Prostaglandins A; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C100008:prostaglandin A2; D015232:Dinoprostone