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ANTAGONISM OF THE THROMBOXANE‐SENSITIVE CONTRACTILE SYSTEMS OF THE RABBIT AORTA, DOG SAPHENOUS VEIN AND GUINEA‐PIG TRACHEA
Author(s) -
JONES R.L.,
PEESAPATI V.,
WILSON N.H.
Publication year - 1982
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1982.tb09236.x
Subject(s) - guinea pig , thromboxane a2 , vein , aorta , rabbit (cipher) , cardiology , medicine , antagonism , thoracic aorta , anatomy , platelet , receptor , statistics , mathematics
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 ω‐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 2α 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.