Distinct stimulatory effect of platelet-activating factor on prostaglandin I2 and thromboxane A2 biosynthesis by rat dental pulp.
Platelet-activating factor (PAF-acether), but not lyso PAF, stimulated the production of both PGI2 and TXA2 by rat dental pulp tissue in vitro. However, there were differences in the dose- and time-dependence of the stimulatory effects. PAF-acether antagonists, Bn 52021, CV 3988 and kadsurenone, dose dependently inhibited PAF-acether-induced PG production. BN 52021, CV 3988 also dose dependently inhibited TX production, but kadsurenone was almost without effect on TX production. Pretreatment of the tissues with PAF-acether or phorbol 12-myristate 13-acetate completely abolished the effect of the second challenge with PAF-acether. The stimulatory effects of PAF-acether and the calcium ionophore A23187 on PGI2 production were completely blocked by removal of extracellular calcium, whereas the effects on TXA2 production were not. TMB-8, an intracellular calcium antagonist, completely inhibited PAF-acether-induced PG production, whereas it slightly inhibited TX production. H-7, a protein kinase C inhibitor, and neomycin, a phospholipase C inhibitor, completely inhibited PAF-acether-induced PG and TX production, whereas W-7, a calmodulin inhibitor, did not. These results suggest that PAF-acether stimulates PGI2 and TXA2 production in rat dental pulp by interacting with distinct PAF-acether receptors, and that these receptors are coupled to independent signal transduction pathways which have a different dependence on extra- and intracellular calcium.
Hirafuji
M
M
Department of Pharmacology, Tohoku University School of Dentistry, Sendai, Japan.
Ogura
Y
Y
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D003782:Dental Pulp / Q000187:drug effects / Q000378:metabolism*; D011464:Epoprostenol / Q000096:biosynthesis*; D066298:In Vitro Techniques; D007700:Kinetics; D008297:Male; D010972:Platelet Activating Factor / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013268:Stimulation, Chemical; D013928:Thromboxane A2 / Q000096:biosynthesis*
D010972:Platelet Activating Factor; D000001:Calcimycin; D013928:Thromboxane A2; D011464:Epoprostenol; D002118:Calcium