Regional distribution of the two subtypes of angiotensin II receptor in rat brain using selective nonpeptide antagonists.
We have demonstrated the existence and localization of two angiotensin II (AII) receptor subtypes in different regions of the rat brain using competitive radioligand binding technique. The identification of the subtypes was made by the reciprocal selectivity of DuP 753 and PD123177 for the AII-1 and AII-2 receptors, respectively. In the pituitary gland, DuP 753 inhibited 95% of the specific AII binding with a Ki value of 1.85 x 10(-9) M while PD123177 had little effect. In the whole brain, thalamus-septum and midbrain, PD123177 inhibited 90% of the specific binding with Ki value of 7.77 x 10(-8) M, 8.21 x 10(-8) M and 4.93 x 10(-8) M, respectively while DuP 753 had little effect. In the hypothalamus, DuP 753 and PD123177 had Ki values of 5.67 x 10(-8) M and 1.60 x 10(-7) M, respectively, for their respective receptor subtypes. In the cerebellum and cerebral cortex, the AII specific binding was low. The data suggest there are at least two subtypes of AII receptor in the rat brain and that they are not uniformly distributed.
Leung
K H
KH
Medical Products Department, E.I. du Pont de Nemours and Company, Wilmington, DE 19880-0400.
Smith
R D
RD
Pieter
Timmermans
B M
BM
Chiu
A T
AT
D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000378:metabolism*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007700:Kinetics; D019808:Losartan; D008297:Male; D009928:Organ Specificity; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000378:metabolism*; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D011725:Pyridines; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C066253:PD 123177; D019808:Losartan