Agonist-antagonist interactions at angiotensin receptors: application of a two-state receptor model

Trends Pharmacol Sci. 1994 Oct;15(10):364-9. doi: 10.1016/0165-6147(94)90156-2.

Abstract

Interactions between agonists and antagonists at angiotensin receptors are characterized by a number of features: variation of antagonist dynamics between apparent simple competition, insurmountable antagonism and, occasionally, augmentation; the tendency for insurmountable antagonism to be saturable; slow recovery of agonist responses following agonist-induced tachyphylaxis; and the ability of competitive antagonists to accelerate recovery from the latter intervention. Some of these phenomena have also been observed in studies of 5-HT2 receptors where they were attributed to the operation of a two-state model with an allosteric site. In this article, Mark Robertson and colleagues propose that the properties of angiotensin AT1 receptors may be explained by a similar model, but without the need to evoke an allosteric site.

Publication types

  • Review

MeSH terms

  • Angiotensin II / antagonists & inhibitors
  • Angiotensin Receptor Antagonists*
  • Animals
  • Biphenyl Compounds / pharmacology
  • Computer Simulation*
  • Drug Interactions
  • Imidazoles / pharmacology
  • Losartan
  • Models, Biological*
  • Receptors, Angiotensin / agonists*
  • Tachyphylaxis
  • Tetrazoles / pharmacology

Substances

  • Angiotensin Receptor Antagonists
  • Biphenyl Compounds
  • Imidazoles
  • Receptors, Angiotensin
  • Tetrazoles
  • Angiotensin II
  • Losartan