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.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology
-
Alprostadil / analogs & derivatives
-
Alprostadil / pharmacology
-
Animals
-
Dinoprostone / analogs & derivatives
-
Dinoprostone / analysis
-
Dinoprostone / pharmacology*
-
Drug Interactions
-
Drug Synergism
-
Femoral Artery / drug effects*
-
In Vitro Techniques
-
Intracellular Signaling Peptides and Proteins
-
Male
-
Nifedipine / pharmacology
-
Phenylephrine / pharmacology*
-
Potassium / pharmacology*
-
Prostaglandins F, Synthetic / pharmacology
-
Protein Serine-Threonine Kinases / antagonists & inhibitors
-
Rats
-
Rats, Sprague-Dawley
-
Receptors, Prostaglandin / agonists
-
Receptors, Prostaglandin / metabolism
-
Receptors, Prostaglandin E / agonists
-
Receptors, Prostaglandin E / antagonists & inhibitors
-
Receptors, Prostaglandin E / metabolism
-
Receptors, Prostaglandin E, EP1 Subtype
-
Receptors, Prostaglandin E, EP3 Subtype
-
Sensitivity and Specificity
-
Sulfonamides / metabolism
-
Vasoconstrictor Agents / pharmacology*
-
rho-Associated Kinases
Substances
-
5-bromo-2-methoxy-N-(3-(naphthalen-2-yl-methylphenyl)acryloyl)benzenesulfonamide
-
Intracellular Signaling Peptides and Proteins
-
Prostaglandins F, Synthetic
-
Ptger1 protein, rat
-
Ptger3 protein, rat
-
Receptors, Prostaglandin
-
Receptors, Prostaglandin E
-
Receptors, Prostaglandin E, EP1 Subtype
-
Receptors, Prostaglandin E, EP3 Subtype
-
Sulfonamides
-
Vasoconstrictor Agents
-
prostaglandin F2alpha receptor
-
SC-46275
-
Phenylephrine
-
fluprostenol
-
sulprostone
-
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
-
Protein Serine-Threonine Kinases
-
rho-Associated Kinases
-
Alprostadil
-
Nifedipine
-
Dinoprostone
-
Potassium