Agonist-antagonist interactions at angiotensin receptors: application of a two-state receptor model.
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.
Robertson
M J
MJ
Department of Pharmacology, Fisons, Loughborough, Leicestershire, UK.
Dougall
I G
IG
Harper
D
D
McKechnie
K C
KC
Leff
P
P
D000804:Angiotensin II / Q000037:antagonists & inhibitors; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D003198:Computer Simulation; D004347:Drug Interactions; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D008954:Models, Biological; D011945:Receptors, Angiotensin / Q000819:agonists*; D013618:Tachyphylaxis; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; D019808:Losartan