EP4 receptor mediation of prostaglandin E2-stimulated mucus secretion by rabbit gastric epithelial cells.
Prostaglandin (PG) E receptors are divided into four subtypes (EP1-EP4). We investigated the EP receptor subtype involved in PGE2-stimulated mucus secretion by rabbit gastric epithelial cells. Northern blot analysis revealed that epithelial cells express EP3 and EP4 receptor mRNAs, but neither EP1 nor EP2 receptor mRNAs were detected. PGE2, 11-deoxy-PGE1 (an EP3/EP4/EP2 agonist) and 16,16-dimethyl-PGE2 (an EP3/EP2/EP4 agonist) concentration-dependently promoted mucus secretion. In contrast, 17-phenyl-PGE2 (an EP3/EP1 agonist), sulprostone (an EP3/EP1 agonist), and butaprost (an EP2 agonist) failed to stimulate secretion. The effective concentrations of PGE2, 11-deoxy-PGE1, and 16,16-dimethyl-PGE2 were associated with their affinities for the EP4 receptor. In addition, PGE2, 11-deoxy-PGE1, and 16,16-dimethyl-PGE2 increased cyclic AMP (cAMP) production, but the other prostanoids had no effect. SQ22536 [9-(tetrahydro-2'-furyl)adenine; an adenylate cyclase inhibitor] inhibited both the increased cAMP production and mucus secretion induced by PGE2, 11-deoxy-PGE1, and 16,16-dimethyl-PGE2. H-89 (N-[2-((p-bromocinnamyl)amino)ethyl]-5-isoquinoline sulfonamide; a protein kinase A inhibitor) also abolished the stimulatory effects of the prostanoids on mucus secretion, but calphostin C (a protein kinase C inhibitor) did not. These results indicate that PGE2 promotes mucus secretion by rabbit gastric epithelial cells, mediated through EP4 receptor stimulation and the subsequent activation of protein kinase A.
Takahashi
S
S
Department of Applied Pharmacology, Kyoto Pharmaceutical University, Japan. takahasi@mb.kyoto-phu.ac.jp
Takeuchi
K
K
Okabe
S
S
D015064:16,16-Dimethylprostaglandin E2 / Q000494:pharmacology; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D002478:Cells, Cultured; D015232:Dinoprostone / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009093:Mucus / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D011817:Rabbits; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000378:metabolism*; D058308:Receptors, Prostaglandin E, EP3 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D015398:Signal Transduction
D012333:RNA, Messenger; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; C017759:9-(tetrahydro-2-furyl)-adenine; D000225:Adenine; D015232:Dinoprostone; D015064:16,16-Dimethylprostaglandin E2