Antagonism of the thromboxane-sensitive contractile systems of the rabbit aorta, dog saphenous vein and guinea-pig trachea

Br J Pharmacol. 1982 Jul;76(3):423-38. doi: 10.1111/j.1476-5381.1982.tb09236.x.

Abstract

1 The thromboxane-sensitive contractile systems in spirally-cut preparations of the rabbit aorta, dog saphenous vein and guinea-pig trachea have been compared. The full or partial agonist activities of a range of bicyclic ring analogues were found to be remarkably similar on the three preparations. In addition, EP 045, a prostanoid with a phenylsemicarbazone omega-chain, blocked the action of both thromboxane A(2) (TXA(2)) and the bicyclic ring analogues. Using 11,9-epoxymethano prostaglandin H(2) as the agonist, linear Schild plots with slopes close to unity were obtained on each preparation; this suggests a competitive type of antagonism.2 Analogues of prostaglandin D(2) (PGD(2)), PGE(2) and PGF(2alpha) also contracted the three smooth muscle preparations; those analogues containing a 16-p-halophenoxy residue were highly active. On the rabbit aorta, EP 045 completely blocked the contractile actions of these agonists, perhaps indicating a single type of prostanoid receptor in this tissue. On the dog saphenous vein PGD(2), PGE(2) and 15-methyl PGE(2) exhibited relaxant activity when the tissue was partially contracted with either a thromboxane agonist or noradrenaline. On the guinea-pig trachea 16,16-dimethyl PGE(2) and the 16-p-chlorophenoxy analogue of PGE(2) were potent contractile agents whose action was not blocked by EP 045. PGE(2) and 15-methyl PGE(2) showed similar properties but exhibited relaxant activity with increasing concentrations in the organ bath. Our results indicate the presence of three types of prostanoid receptors in the guinea-pig trachea: thromboxane- and PGE-sensitive systems mediating contraction and a PGE-sensitive system mediating relaxation.3 The similarity of the thromboxane-sensitive systems in the three smooth muscle preparations is discussed with particular reference to the differences in the equilibrium dissociation constants for EP 045.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / drug effects
  • Dinoprost
  • Dinoprostone
  • Dogs
  • Dose-Response Relationship, Drug
  • Female
  • Guinea Pigs
  • In Vitro Techniques
  • Male
  • Muscle Contraction / drug effects*
  • Muscle, Smooth / drug effects*
  • Prostaglandins D / pharmacology
  • Prostaglandins E / pharmacology
  • Prostaglandins F / pharmacology
  • Prostaglandins H / pharmacology
  • Prostaglandins, Synthetic / pharmacology
  • Rabbits
  • Receptors, Cell Surface / drug effects*
  • Receptors, Prostaglandin / drug effects*
  • Saphenous Vein / drug effects
  • Thromboxane A2 / pharmacology
  • Thromboxanes / antagonists & inhibitors*
  • Trachea / drug effects

Substances

  • Prostaglandins D
  • Prostaglandins E
  • Prostaglandins F
  • Prostaglandins H
  • Prostaglandins, Synthetic
  • Receptors, Cell Surface
  • Receptors, Prostaglandin
  • Thromboxanes
  • Thromboxane A2
  • EP 045
  • Dinoprost
  • Dinoprostone