The existence of distinct classes of prostaglandin E2 receptors mediating adenylate cyclase and phospholipase C pathways in osteoblastic clone MC3T3-E1.
We have reported previously that PGE2 evoked an increase in intracellular calcium level ([Ca2+]i) in mouse osteoblastic cells (1). Here, we investigated the effects of PGE1 and PGF2 alpha on cAMP production and [Ca2+]i in comparison with those of PGE2. In osteoblastic clone, MC3T3-E1 cells, PGE1 stimulated cAMP production, but had no effect on [Ca2+]i, whereas PGF2 alpha evoked only [Ca2+]i increase. In contrast, PGE2 not only stimulated cAMP production, but also increased [Ca2+]i. From the Scatchard plot analysis of PGE2 it was confirmed that there were two classes of PGE2 binding sites (Kd value, 9.2 nM; binding site, 29 fmole/mg protein, and Kd value, 134 nM; binding site, 148 fmole/mg protein). As the increase in [Ca2+]i was caused by PGF2 alpha and PGE2, but not by PGE1, we investigated the displacement of [3H]-PGF2 alpha binding. The displacement capacity of unlabeled PGE2 was about 110 of that of PGF2 alpha, while that of PGE1 was very low even at 500-fold excess. These data indicate the possibility that the dual action of PGE2 is mediated by distinct receptor systems.
Toriyama
K
K
Department of Physiological Chemistry, Faculty of Dentistry, Tokyo Medical and Dental University, Japan.
Morita
I
I
Murota
S
S
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000527:Alprostadil / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002999:Clone Cells / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D015237:Dinoprost / Q000494:pharmacology; D015232:Dinoprostone / Q000378:metabolism* / Q000494:pharmacology; D051379:Mice; D010006:Osteoblasts / Q000378:metabolism*; D011485:Protein Binding; D011982:Receptors, Prostaglandin / Q000145:classification* / Q000187:drug effects / Q000378:metabolism; D018078:Receptors, Prostaglandin E; D015290:Second Messenger Systems; D010738:Type C Phospholipases / Q000378:metabolism*
D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D015237:Dinoprost; D000242:Cyclic AMP; D010738:Type C Phospholipases; D000262:Adenylyl Cyclases; D000527:Alprostadil; D015232:Dinoprostone; D002118:Calcium