Prostaglandin E2 Stimulates EP2, Adenylate Cyclase, Phospholipase C, and Intracellular Calcium Release to Mediate Cyclic Adenosine Monophosphate Production in Dental Pulp Cells

• Published in: Journal of endodontics Vol. 42; no. 4; pp. 584 - 588
• Main Authors: Chang, Mei-Chi, MS, PhD, Lin, Szu-I., DDS, Lin, Li-Deh, DDS, PhD, Chan, Chiu-Po, DDS, MS, Lee, Ming-Shu, DDS, MS, Wang, Tong-Mei, DDS, PhD, Jeng, Po-Yuan, DDS, Yeung, Sin-Yuet, DDS, Jeng, Jiiang-Huei, DDS, PhD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2016
• Subjects: Adenosine Monophosphate - metabolism; Adenylate cyclase; Adenylyl Cyclase Inhibitors - pharmacology; Adenylyl Cyclases - metabolism; calcium; Calcium - metabolism; Calcium Signaling - drug effects; cyclic adenosine monophosphate; Cyclic AMP - biosynthesis; Cyclic AMP - metabolism; Dental Pulp - cytology; Dental Pulp - drug effects; Dental Pulp - metabolism; Dentistry; Dinoprostone - pharmacology; Endocrinology & Metabolism; Humans; prostaglandin; prostaglandin receptor; Prostaglandins - pharmacology; pulp cells; Receptors, Prostaglandin - metabolism; Receptors, Prostaglandin E, EP2 Subtype - agonists; Receptors, Prostaglandin E, EP2 Subtype - metabolism; signal transduction; Type C Phospholipases - metabolism; Adenylate cyclase; calcium; cyclic adenosine monophosphate; pulp cells; prostaglandin; signal transduction; prostaglandin receptor
• ISSN: 0099-2399; 1878-3554
• DOI: 10.1016/j.joen.2015.12.011

Abstract Introduction 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.