Characterization of a prostanoid EP3-receptor in guinea-pig aorta: partial agonist action of the non-prostanoid ONO-AP-324

Br J Pharmacol. 1998 Nov;125(6):1288-96. doi: 10.1038/sj.bjp.0702189.


Contraction of guinea-pig isolated aorta induced by the prostaglandin E analogue sulprostone (1-400 nM) has a lower maximum response (40%) than that of phenylephrine or U-46619 (TP-receptor agonist). A prostanoid EP3-receptor subtype is involved based on agonist potency ranking: equi-effective molar ratios (EMR) are sulprostone (EC50 approximately equal to 23 nM) 1.0, SC-46275 0.11, misoprostol 2.2, gemeprost 3.3, PGE2 5.4, 17-phenyl PGE2 6.0, GR-63799 8.9. GR-63799, which contains a bulky ester group, is relatively more potent on neuronal EP3 preparations than on the aorta. ONO-AP-324, a relative of the non-prostanoid prostacyclin mimetic series, behaves as an EP3 partial agonist on the aorta, inhibiting sulprostone responses but acting synergistically (in a similar manner to sulprostone) with phenylephrine; it may be a useful pharmacological tool for studying EP3-receptors. Sulprostone contractions are markedly suppressed in zero-Ca2+ bathing fluid containing either 2 mM EDTA or 50 microM EGTA, and by Cd2+ (500 microM), but are usually unaffected by nifedipine (0.3 microM) and verapamil (4.44 microM). Influx of Ca2+, but not through L-type Ca2+-channels, appears to be the major contractile mechanism. The guinea-pig aorta is a valuable addition to the vascular EP3 preparations available and may increase our knowledge of the mechanisms whereby Gi-coupled receptors mediate vasoconstriction (c.f. 5-HT1B/D- and alpha2-receptors). The possibility of certain EP3 agonists distinguishing EP3-receptor isoforms is discussed.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology
  • Acetates / pharmacology*
  • Animals
  • Aorta, Thoracic / drug effects
  • Aorta, Thoracic / physiology
  • Aorta, Thoracic / ultrastructure
  • Benzhydryl Compounds / pharmacology*
  • Calcium / metabolism
  • Dinoprostone / analogs & derivatives
  • Dinoprostone / pharmacology
  • Guinea Pigs
  • In Vitro Techniques
  • Male
  • Muscle Contraction / drug effects
  • Muscle Relaxation / drug effects
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / physiology
  • Muscle, Smooth, Vascular / ultrastructure*
  • Oxytocics / pharmacology
  • Pulmonary Artery / drug effects
  • Pulmonary Artery / physiology
  • Pulmonary Artery / ultrastructure
  • Receptors, Prostaglandin E / agonists*
  • Receptors, Prostaglandin E, EP3 Subtype
  • Vas Deferens / drug effects
  • Vas Deferens / physiology
  • Vas Deferens / ultrastructure
  • Vasoconstrictor Agents / pharmacology


  • Acetates
  • Benzhydryl Compounds
  • ONO AP 324
  • Oxytocics
  • Receptors, Prostaglandin E
  • Receptors, Prostaglandin E, EP3 Subtype
  • Vasoconstrictor Agents
  • sulprostone
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • Dinoprostone
  • Calcium