Angiotensin II receptor subtypes in rat brain.
1. Angiotensin II (AII) receptor binding was localized in the rat brain by in vitro autoradiography using the antagonist analogue, 125I-[Sar1, Ile8] AII. AII receptor binding was then differentiated into type I and type II subtypes by displacement with unlabelled non-peptide antagonists specific for AII subtypes. 2. Type I binding was determined as that inhibited by Dup753 (10 mumol/L) and type II binding as that inhibited by XD329-1 (10 mumol/L). The reducing agent dithiothreitol (DTT) decreased the binding to type I receptors and enhanced the binding to type II receptors. 3. Structures such as the vascular organ of the lamina terminalis, subfornical organ, median preoptic nucleus, area postrema, nucleus of the solitary tract, which are known to be related to some central actions of AII, contain exclusively type I AII receptors. 4. In contrast, the locus coeruleus, ventral and dorsal parts of lateral septum, superior colliculus, subthalamic nucleus, some nuclei of the thalamus, and the nuclei of the inferior olive contain predominantly type II AII receptors. 5. These results reveal important pharmacological heterogeneity of brain AII receptors which suggest different regional functions and are relevant to the central actions of emerging classes of new non-peptide AII receptor antagonists.
Song
K
K
Department of Medicine, Austin Hospital, University of Melbourne, Heidelberg, Victoria, Australia.
Allen
A M
AM
Paxinos
G
G
Mendelsohn
F A
FA
D015059:1-Sarcosine-8-Isoleucine Angiotensin II; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D011869:Radioligand Assay; D051381:Rats; D011919:Rats, Inbred Strains; D011945:Receptors, Angiotensin / Q000032:analysis*
D011945:Receptors, Angiotensin; D015059:1-Sarcosine-8-Isoleucine Angiotensin II