title: Investigation of the pronounced synergism between prostaglandin E2 and other constrictor agents on rat femoral artery.
abstract: This study investigates the pronounced synergism between the weak contractile action of prostaglandin E(2) (PGE(2)) and strong actions of phenylephrine, U-46619 and K(+) on rat isolated femoral artery. The potency ranking for synergism was SC-46275 (prostanoid receptor agonist selectivity: EP(3)>>EP(1))=sulprostone (EP(3)>EP(1))>17-phenyl PGE(2) (EP(1)>EP(3)). The novel EP(3) antagonist L-798106 (0.2-1microM) blocked the enhanced action of sulprostone (pA(2)=7.35-8.10), while the EP(1) antagonist SC-51322 (1microM) did not (pA(2)<6.0). Matching responses to priming agent and priming agent/sulprostone were similarly suppressed by nifedipine (300nM) and the selective Rho-kinase inhibitors H-1152 (0.1-1microM) and Y-27632 (1-10microM). Our findings implicate an EP(3) receptor in the prostanoid component of contractile synergism. While the synergism predominantly operates through a Ca(2+) influx-Rho-kinase pathway, the EP(3) receptor does not necessarily transduce via Rho-kinase.
authors.affiliation: Department of Pharmacology, Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
authors.forename: Gloria H Y
authors.initials: GH
authors.lastname: Hung
authors.forename: Robert Leslie
authors.initials: RL
authors.lastname: Jones
authors.forename: Francis F Y
authors.initials: FF
authors.lastname: Lam
authors.forename: Kam-Ming
authors.initials: KM
authors.lastname: Chan
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Hidaka
authors.forename: Masaaki
authors.initials: M
authors.lastname: Suzuki
authors.forename: Yasuharu
authors.initials: Y
authors.lastname: Sasaki
mesh_terms: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000527:Alprostadil / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D015232:Dinoprostone / Q000031:analogs & derivatives / Q000032:analysis / Q000494:pharmacology*; D004347:Drug Interactions; D004357:Drug Synergism; D005263:Femoral Artery / Q000187:drug effects*; D066298:In Vitro Techniques; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology*; D011188:Potassium / Q000494:pharmacology*; D011461:Prostaglandins F, Synthetic / Q000494:pharmacology; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D011982:Receptors, Prostaglandin / Q000819:agonists / Q000378:metabolism; D018078:Receptors, Prostaglandin E / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D012680:Sensitivity and Specificity; D013449:Sulfonamides / Q000378:metabolism; D014662:Vasoconstrictor Agents / Q000494:pharmacology*; D054460:rho-Associated Kinases; D000096926:Benzenesulfonamides
chemical_list: D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000527:Alprostadil; D015232:Dinoprostone; D047908:Intracellular Signaling Peptides and Proteins; D009543:Nifedipine; D010656:Phenylephrine; D011188:Potassium; D011461:Prostaglandins F, Synthetic; D017346:Protein Serine-Threonine Kinases; D011982:Receptors, Prostaglandin; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D013449:Sulfonamides; D014662:Vasoconstrictor Agents; D054460:rho-Associated Kinases; C000595268:5-bromo-2-methoxy-N-(3-(naphthalen-2-yl-methylphenyl)acryloyl)benzenesulfonamide; D000096926:Benzenesulfonamides; C545637:Ptger1 protein, rat; C545649:Ptger3 protein, rat; C034671:prostaglandin F2alpha receptor; C072122:SC-46275; C006326:fluprostenol; C016767:sulprostone