Antagonist-AT1 interactions: elucidation of a novel molecular mechanism.

Project Details

Description

Non-peptidic AT1 receptor antagonists have been developed to combat hyptension and their properties have often been studied by in vitro contraction experiments with rabbit aortic strips. Insurmountable antagonists decreased the maximale response to AII, either partially or almost totally. Several theories have been advanced to explain ths difference and, in this context, we obtaines new inforamtion by measuring AII-induced inositol phosphate production in CHO-AT1 cells. All antagonists were found to inhibit the AII-mediated response in a competitive fashion and the insurmountable behaviour of candesartan in preincubation experiments was related its long-lasting binding to the receptor. The existence of a fast reversible and a tight binding state of the antagonist - AT1receptor complex was unveiled as well. this may explain the only partial insurmountable effect of certain antagonists. the aim of the present study is to the investigate the molecular significance of the two states of the antagonist - AT1 receptor complex.
AcronymFWOAL166
StatusFinished
Effective start/end date1/01/0131/12/06

Keywords

  • blood pressure
  • angiotensin
  • mechanism
  • receptors
  • antagonists

Flemish discipline codes

  • Biological sciences
  • Pharmaceutical sciences