Analysis of the antagonist profile of SK&F 88046 on guinea pig trachea.
SK&F 88046 preferentially antagonized the contractions elicited by the functional thromboxane (Tx) A2 mimics and structural endoperoxide analogs, U-44069 and U-46619, on the guinea pig trachea. This concentration-dependent antagonism was described by pA2 values of 7.03 against U-46619 and 6.97 against U-44069; the slopes of both Schild plots were 0.9. Whereas SK&F 88046 did not antagonize the tracheal contractions elicited by leukotriene (LT) C4 or D4, carbachol or histamine, this agent did antagonize the contractions induced by carbocyclic thromboxane A2 (CTA2) and prostaglandin (PG) F2 alpha and D2. At 1 X 10(-5)M SK&F 88046, the antagonism was described by -log KB values of 5.9 for CTA2, 5.5 for PGF2 alpha, and 6.4 for PGD2. Thus, SK&F 88046 was 3 to 20-fold more potent an antagonist of U-44069 and U-46619, suggesting that SK&F 88046 may function primarily as a thromboxane/endoperoxide antagonist on the guinea pig trachea.
D000818:Animals; D006168:Guinea Pigs; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D011448:Prostaglandin Antagonists / Q000494:pharmacology*; D013189:SRS-A / Q000037:antagonists & inhibitors; D013449:Sulfonamides / Q000494:pharmacology*; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D013931:Thromboxanes / Q000037:antagonists & inhibitors*; D014132:Trachea / Q000502:physiology
D011448:Prostaglandin Antagonists; C034339:SK&F 88046; D013189:SRS-A; D013449:Sulfonamides; D013931:Thromboxanes; D013928:Thromboxane A2