Characterization of receptors involved in the direct and indirect actions of prostaglandins E and I on the guinea-pig ileum

Br J Pharmacol. 1992 Feb;105(2):271-8. doi: 10.1111/j.1476-5381.1992.tb14245.x.


1. A study of the effects of prostaglandin E2 (PGE2) and eleven synthetic analogues on the guinea-pig isolated ileum preparation has revealed three distinct contractile actions, each associated with a different prostaglandin E (EP-) receptor subtype. In addition, PGI2 (prostacyclin) and its stable analogues can activate prostaglandin I (IP-) receptors to elicit both contraction and relaxation of the ileum. 2. Two of the PGE actions involve direct stimulation of the smooth muscle, being unaffected by 1 microM morphine treatment. One action is blocked by AH 6809 at micromolar concentrations and ICI 80205 and 16,16-dimethyl PGE2 are particularly potent agonists. Activation of EP1-receptors appears to be involved. The second action is unaffected by AH 6809; sulprostone and MB 28767 are potent agonists. Comparison with agonist potency rankings on the guinea-pig vas deferens indicates that EP3-receptors may be involved. 3. The third PGE effect and the stimulant PGI effect are blocked by morphine, indicating enteric neurones and/or sensory nerve terminals as sites of action. EP2-receptors may be involved in the PGE action, in view of the marked effect of morphine on the contractile actions of misoprostol, 11-deoxy PGE2-1-alcohol, 11-deoxy PGE1 and butaprost, all of which show some selectivity for EP2-receptors. The PGI action is most easily studied with cicaprost (EC25 = 1.3 nM), since iloprost, carbacyclin and to a lesser extent PGI2 also have agonist activity at EP1-receptors. 4. The contractile action of 17-phenyl-omega-trinor PGE2 on the ileum is unaffected by morphine. Since this analogue shows only weak agonist activity on the rabbit jugular vein (EP2 preparation) and guinea-pig vas deferens (EP3), it may be a more useful standard agonist than PGE2 in EPl1-receptor studies.5. In the presence of morphine and AH 6809, cicaprost inhibits histamine-induced contractions (IC25 = 22 nM). PGI2 and iloprost show mixed inhibitory/potentiating actions, whereas carbacyclin only potentiates histamine contractions. This IP-receptor-mediated inhibition may account for the bell-shaped log concentration-response curve of cicaprost (no inhibitors present) and the very marked block of iloprostinduced contractions by AH 6809.6. We have found no evidence for either IP-receptors mediating direct contraction or EP-receptors mediating inhibition of the ileum longitudinal smooth muscle, as has been suggested in the literature.7. In view of the complexity of prostanoid action on the guinea-pig ileum we feel that the preparation must be used with caution to ascertain the EPl agonist or antagonist potencies of novel compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Epoprostenol / analogs & derivatives
  • Epoprostenol / antagonists & inhibitors
  • Epoprostenol / metabolism
  • Epoprostenol / pharmacology*
  • Guinea Pigs
  • Histamine Antagonists / pharmacology
  • Ileum / drug effects
  • In Vitro Techniques
  • Male
  • Morphine / pharmacology
  • Muscle Relaxation / drug effects
  • Prostaglandin Antagonists / pharmacology
  • Prostaglandins E / antagonists & inhibitors
  • Prostaglandins E / metabolism
  • Prostaglandins E / pharmacology*
  • Prostaglandins E, Synthetic / pharmacology
  • Receptors, Prostaglandin / antagonists & inhibitors
  • Receptors, Prostaglandin / drug effects
  • Receptors, Prostaglandin / physiology*
  • Trachea / drug effects
  • Vas Deferens / drug effects
  • Xanthenes / pharmacology
  • Xanthones*


  • Histamine Antagonists
  • Prostaglandin Antagonists
  • Prostaglandins E
  • Prostaglandins E, Synthetic
  • Receptors, Prostaglandin
  • Xanthenes
  • Xanthones
  • 6-isopropoxy-9-oxoxanthene-2-carboxylic acid
  • carboprostacyclin
  • Morphine
  • Epoprostenol