Inhibitory prostanoid EP receptors in human non-pregnant myometrium.
Prostanoid EP receptor agonists relaxed cloprostenol-stimulated contraction of human non-pregnant myometrium in vitro with pEC50 values of (n = 4): prostaglandin E2, 7.8+/-0.2 > 1-OH prostaglandin E1, 7.2+/-0.3 > misoprostol, 6.6+/-0.1 > 16,16-dimethyl prostaglandin E2, 6.3+/-0.7 > butaprost, 5.7+/-0.3 > 11-deoxy prostaglandin E1, 5.5+/-0.2 = AH13205 ((+)-trans-2-[4-(1hydroxyhexyl)phenyl]-5-oxocyclopentaneheptano ic acid), 5.5+/-0.2. The EP4 receptor antagonist AH23848B ([1alpha(z), 2beta5alpha]-(+/-)-7-[5-[[(1,1'-biphenyl)-4-yl]methoxy]-2-(4-morph olinyl)-3-oxo-cyclopentyl]-4-heptenoic acid) (29 microM) had no effect on concentration-effect curves to the EP receptor agonists. The mixed prostanoid receptor antagonist AH6809 (6-isopropoxy-9-oxaxanthene-2-carboxylic acid) competitively antagonised prostaglandin E2 with a pA2 of 5.6+/-0.2. AH6809 (42 microM) antagonised misoprostol, 11-deoxy prostaglandin E1, and the prostanoid DP receptor agonist BW245C (5-(6-carboxyhexyl)-1-(3-cyclohexyl-3-hydroxypropyl)hydantoin) with apparent pA2 values of 5.6+/-0.3, 5.1+/-0.9 and 5.9+/-0.4 (n = 4), respectively, but was ineffective against the IP receptor agonist cicaprost (n = 4). The prostanoid DP receptor antagonist BW A868C (3-benzyl-5-(6-carboxyhexyl)-1-(2-cyclohexyl-2-hydroxyethylamino)h ydantoin) (50 nM) had no effect on responses to prostaglandin E2 or misoprostol. The presence of an AH6809-sensitive, AH23848B- and BW A868C-insensitive mechanism is consistent with the hypothesis that inhibitory EP receptor agonists cause relaxation of human non-pregnant myometrium by an EP2 receptor-mediated process.
Hillock
C J
CJ
Honours Biology and Pharmacology Programme, McMaster University, Hamilton, Ontario, Canada.
Crankshaw
D J
DJ
D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D066298:In Vitro Techniques; D009126:Muscle Relaxation / Q000187:drug effects; D009215:Myometrium / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D011448:Prostaglandin Antagonists / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology*; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism*; D058307:Receptors, Prostaglandin E, EP2 Subtype; D014966:Xanthenes / Q000494:pharmacology*; D044004:Xanthones
D000889:Anti-Arrhythmia Agents; D001713:Biphenyl Compounds; C545644:PTGER2 protein, human; D011448:Prostaglandin Antagonists; D011453:Prostaglandins; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D014966:Xanthenes; D044004:Xanthones; C053876:6-isopropoxy-9-oxoxanthene-2-carboxylic acid; C046926:AH 23848