Antagonism of the thromboxane-sensitive contractile systems of the rabbit aorta, dog saphenous vein and guinea-pig trachea.
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.
D000818:Animals; D001011:Aorta / Q000187:drug effects; D015237:Dinoprost; D015232:Dinoprostone; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D011457:Prostaglandins D / Q000494:pharmacology; D011458:Prostaglandins E / Q000494:pharmacology; D011460:Prostaglandins F / Q000494:pharmacology; D011463:Prostaglandins H / Q000494:pharmacology; D011465:Prostaglandins, Synthetic / Q000494:pharmacology; D011817:Rabbits; D011956:Receptors, Cell Surface / Q000187:drug effects*; D011982:Receptors, Prostaglandin / Q000187:drug effects*; D012501:Saphenous Vein / Q000187:drug effects; D013928:Thromboxane A2 / Q000494:pharmacology; D013931:Thromboxanes / Q000037:antagonists & inhibitors*; D014132:Trachea / Q000187:drug effects
D011457:Prostaglandins D; D011458:Prostaglandins E; D011460:Prostaglandins F; D011463:Prostaglandins H; D011465:Prostaglandins, Synthetic; D011956:Receptors, Cell Surface; D011982:Receptors, Prostaglandin; D013931:Thromboxanes; D013928:Thromboxane A2; C034549:EP 045; D015237:Dinoprost; D015232:Dinoprostone