Quantitative autoradiography reveals different angiotensin II receptor subtypes in selected rat brain nuclei.
Heterogeneity of rat brain angiotensin II receptors was revealed by quantitative autoradiography after incubation with 125I-Sar1-angiotensin II and displacement with the angiotensin II antagonists CGP 42112 A and DuP-753 and by receptor sensitivity to dithiothreitol. Receptors in areas involved in cardiovascular and fluid control--the subfornical organ, nucleus of the solitary tract, paraventricular nucleus, and area postrema--are displaced by DuP-753 with an IC50 of 1 x 10(-7) M, are sensitive to 5 mM dithiothreitol, and thus are angiotensin II type-1. Receptors in the inferior olive are displaced by CGP 42112 A (IC50, 1 x 10(-9) M) but not by DuP-753 in concentrations up to 10(-4) M, are insensitive to 5 mM dithiothreitol, and thus are angiotensin II type-2.
Tsutsumi
K
K
Section on Pharmacology, Laboratory of Clinical Science, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892.
Saavedra
J M
JM
D000804:Angiotensin II / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D001923:Brain Chemistry; D004229:Dithiothreitol / Q000494:pharmacology; D007093:Imidazoles / Q000378:metabolism; D019808:Losartan; D008297:Male; D008526:Medulla Oblongata / Q000737:chemistry / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism; D010286:Paraventricular Hypothalamic Nucleus / Q000737:chemistry / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000032:analysis* / Q000378:metabolism; D013356:Subfornical Organ / Q000737:chemistry / Q000378:metabolism; D013777:Tetrazoles / Q000378:metabolism; D014018:Tissue Distribution
D057911:Angiotensin Receptor Antagonists; D007093:Imidazoles; D009842:Oligopeptides; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; C060894:CGP 42112A; C041007:angiotensin II, Sar(1)-Val(5)-; D019808:Losartan; D004229:Dithiothreitol