The strong contractile effect of the thromboxane receptor agonist U-46619 in isolated human pulmonary arteries and its competitive antagonism by BM-13.505.
Ring segments (I mm in diameter) of the pulmonary artery obtained from 16 patients undergoing thoracic surgery were mounted in tissue baths. Cumulative concentration-response curves of some prostanoids and amines were obtained, and Emax and pEC50 values calculated. Noradrenaline, phenylephrine, clonidine and serotonin (5-HT) showed low intrinsic activities. Prostaglandin F2 alpha (PGF2 alpha) induced strong contractions with an Emax of 126% of the preceding K+ (124 mM)-induced contraction, but its potency was low (pEC50 = 5.70). The thromboxane receptor agonists U-46619 and U-44069 induced strong contractions (Emax = 139% and 133% respectively) and were significantly more potent than the other drugs used (pEC50 = 8.43 and 8.30 respectively). The thromboxane receptor antagonist BM-13.505 (10(-8) to 10(-6) M) caused rightward parallel shifts of the U-46619 concentration-response curves without reduction of Emax, indicating competitive antagonism.
Sjöberg
T
T
Department of Cardiothoracic Surgery, University Hospital of Lund, Sweden.
Steen
S
S
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010648:Phenylacetates / Q000494:pharmacology*; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000187:drug effects; D011982:Receptors, Prostaglandin / Q000187:drug effects*; D017482:Receptors, Thromboxane; D013449:Sulfonamides / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects*
D010648:Phenylacetates; D011450:Prostaglandin Endoperoxides, Synthetic; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013449:Sulfonamides; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C051762:daltroban