Interspecies differences in thromboxane receptors: studies with thromboxane receptor antagonists in rat and guinea pig smooth muscles.
To investigate possible subclasses of thromboxane receptors in vascular and airways smooth muscles, we evaluated activities of five structurally different competitive thromboxane receptor antagonists (i.e., SQ 29,548 [( 1S-[1 alpha, 2 alpha(5Z), 3 alpha, 4 alpha]]-7-[3- [2- [(phenylamino)carbonyl]hydrazino]methyl]-7-oxabicyclo[2.2.1] hept-2-yl]-5-heptenoic acid), L655,240 (3-[1-(4-chlorobenzyl)-5- fluoro-3-methylindol-2yl]2,2-dimethyl propanoic acid), BM 13,505 (4-[2-[[(4-chlorophenyl)sulfonyl]amino]ethyl]benzeneacetic acid), GR 32,191 [( 1R-[1 alpha (Z), 2 beta, 3 beta, 5 alpha]]-(+)-7- [5-[[(1, 1'-biphenyl)-4-yl]methoxy]-3-hydroxy-2-(1- piperidinyl)cyclopentyl]-4-heptenoic acid hydrochloride] and SQ 30,741 [1S- [1 alpha,2 alpha(5Z),3 alpha,4 alpha]]- 7[[[[[( oxaheptyl)amino]acetyl]amino]methyl]- 7-oxabicyclo[2.2.1]hept-2-yl]-5-heptenoic acid)] in trachea, aorta and portal vein from both rats and guinea pigs. Schild plots and drug receptor dissociation constants (KB) were determined for each antagonist in each tissue using U-46,619 as the agonist. Rank orders of potency were identical in rat aorta, rat trachea and rat portal vein (SQ 29,548 greater than L 655,240 greater than BM 13,505 greater than GR 32,191 greater than SQ 30,741), with calculated KB values ranging from 0.5 to 20 nM. Rank orders of potency in guinea pig trachea and guinea pig portal vein were the same (GR 32,191 greater than SQ 29,548 greater than SQ 30,741 greater than L 655,240 greater than BM 13,505), with KB values ranging from 0.1 to 30 nM.(ABSTRACT TRUNCATED AT 250 WORDS)
Ogletree
M L
ML
Pharmacology Department, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, New Jersey.
Allen
G T
GT
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D019086:Bridged Bicyclo Compounds, Heterocyclic; D004336:Drug Antagonism; D005231:Fatty Acids, Unsaturated; D006538:Heptanoic Acids / Q000494:pharmacology; D006834:Hydrazines / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D010648:Phenylacetates / Q000494:pharmacology; D011450:Prostaglandin Endoperoxides, Synthetic / Q000494:pharmacology; D051381:Rats; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017482:Receptors, Thromboxane; D013045:Species Specificity; D013449:Sulfonamides / Q000494:pharmacology; D013928:Thromboxane A2 / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000494:pharmacology
D001713:Biphenyl Compounds; D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006538:Heptanoic Acids; D006834:Hydrazines; D007211:Indoles; D010648:Phenylacetates; D011450:Prostaglandin Endoperoxides, Synthetic; D011982:Receptors, Prostaglandin; D017482:Receptors, Thromboxane; D013449:Sulfonamides; C052517:L 655240; C054215:SQ 30741; D013928:Thromboxane A2; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; C045749:SQ 29548; C060013:vapiprost; C051762:daltroban