Signaling pathways leading to prostaglandin E(2) production by rat cerebral frontal cortex.
In this paper, we have determined the effect of both muscarinic acetylcholine receptor (mAChR) and exogenous prostaglandin E(2) (PGE(2)) on PGE(2) production and cyclooxygenases (COX) mRNA gene expression on rat cerebral frontal cortex. Carbachol and PGE(2) increase endogenous PGE(2) production and the COX-1 mRNA levels by activation of PLA(2)s. The COX-1 and COX-2 activity participated in the production of PGE(2) triggered by exogenous PGE(2). While in carbachol-PGE(2) only COX-1 activity is affected. The specific inhibition of PGE(2) receptor was able to impair the increase of endogenous PGE(2) production triggered by both carbachol and exogenous PGE(2). These results suggest that carbachol-activation mAChR increased PGE(2) production that in turn interacting with its own receptor triggers an additional production of PGE(2). Both mechanisms appear to occur by using PLA(2) signaling system. This data should be able to contribute to understand the involvement of PGE(2) in normal brain function and its participation in neuroinflammatory processes.
Pharmacology Unit, School of Dentistry, University of Buenos Aires, Argentina.
B
B
Orman
S
S
Reina
L
L
Sterin-Borda
E
E
Borda
D000818:Animals; D002217:Carbachol / Q000378:metabolism / Q000494:pharmacology; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism*; D051545:Cyclooxygenase 1 / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D005625:Frontal Lobe / Q000166:cytology / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011976:Receptors, Muscarinic / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
D008565:Membrane Proteins; D012333:RNA, Messenger; D011976:Receptors, Muscarinic; D002217:Carbachol; D051545:Cyclooxygenase 1; C496513:Ptgs1 protein, rat; D010741:Phospholipases A; D015232:Dinoprostone