Nitric oxide synthase and PGE2 reciprocal interactions in rat dental pulp: cholinoceptor modulation.
In this study we determined the effect of cholinoceptor agonist pilocarpine on the stimulation of nitric oxide synthase (NOS) and on prostaglandin E2 (PGE2) generation upon rat dental pulp. By reverse transcriptase/polymerase chain reaction (RT-PCR) we identified several products corresponding to m1, m2, m3, and m4 muscarinic acetylcholine receptors (mAChRs). The stimulation of M1, M2, M3, and M4 mAChRs by pilocarpine increases NOS activity and PGE2 generation. There is a correlation (correlation coefficient=0.05) between NOS activity and PGE2 generation through the activation of phosphoinositide by phospholipase C (PLC), phospholipase A2 (PLA2), and cyclooxygenase 1 (COX-1). Exogenous PGE2 restored NOS activity inhibited by indomenthacin (INDO), whereas nitric oxide (NO) donor restored PGE2 generation inhibited by NG-methyl-L-arginine acetate salt (L-NMMA). These data indicate that both NO and PGE2 interact with their own respective biosynthetic pathways modulating NOS and COX activities. Results could contribute to understanding the involvement of NO and PGE2 in healthy dental pulp given that cellular signals through the parasympathetic system modulate the function of the dentin-pulp complex.
Borda
Enri
E
Pharmacology Unit, School of Dentistry, University of Buenos Aires, and Argentine National Research Council (CONICET), Buenos Aires, Argentina. enri@farmaco.odon.uba.ar
Furlan
César
C
Orman
Betina
B
Reina
Silvia
S
Sterin-Borda
Leonor
L
D000704:Analysis of Variance; D000818:Animals; D053898:Biosynthetic Pathways; D051545:Cyclooxygenase 1 / Q000378:metabolism; D003782:Dental Pulp / Q000187:drug effects / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D004789:Enzyme Activation; D007527:Isoenzymes; D018721:Muscarinic Agonists / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D010862:Pilocarpine / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018709:Statistics, Nonparametric; D015854:Up-Regulation
D007527:Isoenzymes; D018721:Muscarinic Agonists; D011976:Receptors, Muscarinic; D010862:Pilocarpine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D051545:Cyclooxygenase 1; D015232:Dinoprostone