Distinct effects of z-335, a new thromboxane A2 receptor antagonist, on rabbit platelets and aortic smooth muscle

Pharmacology. 2007;79(1):50-6. doi: 10.1159/000097632. Epub 2006 Nov 30.

Abstract

The effect of a novel thromboxane A2 receptor (TP) antagonist, (+/-)-sodium[2-(4-chlorophenylsulfonylaminomethyl)- indan-5-yl]acetate monohydrate (Z-335), on the U46619-induced responses was compared between rabbit platelets and aorta. Z-335 inhibited platelet shape change induced by U46619 with higher efficacy than SQ29548, a common TP antagonist. The U46619-induced platelet aggregation was inhibited by Z-335 in a noncompetitive manner, while it was competitively inhibited by SQ29548. Z-335 inhibited U46619-induced vasoconstriction of rabbit aorta with higher efficacy than SQ29548. The pA2 value of Z-335 in aortic vasoconstriction was significantly higher than in platelet shape change. The competitive binding study showed the higher pKi value of Z-335 against [3H]-SQ29548 binding in rabbit aortic smooth muscle cells than in platelets. These data suggest that Z-335 has useful characteristics of TP antagonism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / pharmacology
  • Angiotensin II / pharmacology
  • Animals
  • Aorta, Thoracic / drug effects*
  • Aorta, Thoracic / physiology
  • Blood Platelets / cytology
  • Blood Platelets / drug effects*
  • Blood Platelets / metabolism
  • Bridged Bicyclo Compounds, Heterocyclic
  • Cell Shape / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Endothelins / pharmacology
  • Fatty Acids, Unsaturated
  • Hydrazines / metabolism
  • Hydrazines / pharmacology
  • In Vitro Techniques
  • Indans / pharmacology*
  • Inositol Phosphates / metabolism
  • Male
  • Muscle, Smooth, Vascular / cytology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology
  • Norepinephrine / pharmacology
  • Platelet Aggregation / drug effects
  • Rabbits
  • Radioligand Assay
  • Receptors, Thromboxane A2, Prostaglandin H2 / antagonists & inhibitors*
  • Tritium
  • Vasoconstriction / drug effects
  • Vasoconstrictor Agents / pharmacology

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • Endothelins
  • Fatty Acids, Unsaturated
  • Hydrazines
  • Indans
  • Inositol Phosphates
  • Receptors, Thromboxane A2, Prostaglandin H2
  • Vasoconstrictor Agents
  • Z 335
  • Tritium
  • Angiotensin II
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • SQ 29548
  • Norepinephrine