title: Prostaglandin E2 Stimulates EP2, Adenylate Cyclase, Phospholipase C, and Intracellular Calcium Release to Mediate Cyclic Adenosine Monophosphate Production in Dental Pulp Cells.
abstract: BACKGROUND
  Prostaglandin E2 (PGE2) plays a crucial role in pulpal inflammation and repair. However, its induction of signal transduction pathways is not clear but is crucial for future control of pulpal inflammation.
  
  
  METHODS
  Primary dental pulp cells were exposed to PGE2 and 19R-OH PGE2 (EP2 agonist) or sulprostone (EP1/EP3 agonist) for 5 to 40 minutes. Cellular cyclic adenosine monophosphate (cAMP) levels were measured using the enzyme-linked immunosorbent assay. In some experiments, cells were pretreated with SQ22536 (adenylate cyclase inhibitor), H89 (protein kinase A inhibitor), dorsomorphin (adenosine monophosphate-activated protein kinase inhibitor), U73122 (phospholipase C inhibitor), thapsigargin (inhibitor of intracellular calcium release), W7 (calmodulin antagonist), verapamil (L-type calcium channel blocker), and EGTA (extracellular calcium chelator) for 20 minutes before the addition of PGE2.
  
  
  RESULTS
  PGE2 and 19R-OH PGE2 (EP2 agonist) stimulated cAMP production, whereas sulprostone (EP1/EP3 agonist) shows little effect. PGE2-induced cAMP production was attenuated by SQ22536 and U73122 but not H89 and dorsomorphin. Intriguingly, thapsigargin and W7 prevented PGE2-induced cAMP production, but verapamil and EGTA showed little effect.
  
  
  CONCLUSIONS
  These results indicate that PGE2-induced cAMP production is associated with EP2 receptor and adenylate cyclase activation. These events are mediated by phospholipase C, intracellular calcium release, and calcium-calmodulin signaling. These results are helpful for understanding the role of PGE2 in pulpal inflammation and repair and possible future drug intervention.
authors.affiliation: Biomedical Science Team and Research Center for Industry of Human Ecology and Graduate Institute of Health Industry Technology, Chang-Gung University of Science and Technology and Chang Gung Memorial Hospital, Taoyuan, Taiwan.
authors.forename: Mei-Chi
authors.initials: MC
authors.lastname: Chang
authors.affiliation: Laboratory of Dental Pharmacology, Toxicology and Pulp Biology, School of Dentistry and Department of Dentistry, National Taiwan University Medical College and National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Szu-I
authors.initials: SI
authors.lastname: Lin
authors.affiliation: Laboratory of Dental Pharmacology, Toxicology and Pulp Biology, School of Dentistry and Department of Dentistry, National Taiwan University Medical College and National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Li-Deh
authors.initials: LD
authors.lastname: Lin
authors.affiliation: Department of Dentistry, Chang Gung Memorial Hospital, Taipei, Taiwan.
authors.forename: Chiu-Po
authors.initials: CP
authors.lastname: Chan
authors.affiliation: Laboratory of Dental Pharmacology, Toxicology and Pulp Biology, School of Dentistry and Department of Dentistry, National Taiwan University Medical College and National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Ming-Shu
authors.initials: MS
authors.lastname: Lee
authors.affiliation: Laboratory of Dental Pharmacology, Toxicology and Pulp Biology, School of Dentistry and Department of Dentistry, National Taiwan University Medical College and National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Tong-Mei
authors.initials: TM
authors.lastname: Wang
authors.affiliation: School of Dentistry, University of Cardenal Herrera, CEU, Valencia, Spain.
authors.forename: Po-Yuan
authors.initials: PY
authors.lastname: Jeng
authors.affiliation: Department of Dentistry, Chang Gung Memorial Hospital, Taipei, Taiwan.
authors.forename: Sin-Yuet
authors.initials: SY
authors.lastname: Yeung
authors.affiliation: Laboratory of Dental Pharmacology, Toxicology and Pulp Biology, School of Dentistry and Department of Dentistry, National Taiwan University Medical College and National Taiwan University Hospital, Taipei, Taiwan. Electronic address: jhjeng@ntu.edu.tw.
authors.forename: Jiiang-Huei
authors.initials: JH
authors.lastname: Jeng
mesh_terms: D000249:Adenosine Monophosphate / Q000378:metabolism; D000067956:Adenylyl Cyclase Inhibitors / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D000242:Cyclic AMP / Q000096:biosynthesis* / Q000378:metabolism*; D003782:Dental Pulp / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D015232:Dinoprostone / Q000494:pharmacology*; D006801:Humans; D011453:Prostaglandins / Q000494:pharmacology; D011982:Receptors, Prostaglandin / Q000378:metabolism; D058307:Receptors, Prostaglandin E, EP2 Subtype / Q000819:agonists / Q000378:metabolism*; D010738:Type C Phospholipases / Q000378:metabolism*
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; C545644:PTGER2 protein, human; D011453:Prostaglandins; D011982:Receptors, Prostaglandin; D058307:Receptors, Prostaglandin E, EP2 Subtype; D000249:Adenosine Monophosphate; D000242:Cyclic AMP; D010738:Type C Phospholipases; D000262:Adenylyl Cyclases; D015232:Dinoprostone; D002118:Calcium
keywords: Adenylate cyclase; calcium; cyclic adenosine monophosphate; prostaglandin; prostaglandin receptor; pulp cells; signal transduction