Investigation of the pronounced synergism between prostaglandin E2 and other constrictor agents on rat femoral artery.
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.
Hung
Gloria H Y
GH
Department of Pharmacology, Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
Jones
Robert Leslie
RL
Lam
Francis F Y
FF
Chan
Kam-Ming
KM
Hidaka
Hiroyoshi
H
Suzuki
Masaaki
M
Sasaki
Yasuharu
Y
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
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