Investigation of the pronounced synergism between prostaglandin E2 and other constrictor agents on rat femoral artery

Prostaglandins Leukot Essent Fatty Acids. 2006 Jun;74(6):401-15. doi: 10.1016/j.plefa.2006.04.002.

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