Premium
Binding of angiotensin antagonists to rat liver and brain membranes measured ex vivo
Author(s) -
Marshall Fiona H.,
Clark Samantha A.,
Michel Anton D.,
Barnes Julie C.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb13639.x
Subject(s) - ex vivo , membrane , in vivo , angiotensin ii , pharmacology , chemistry , endocrinology , medicine , neuroscience , biology , biochemistry , receptor , in vitro , microbiology and biotechnology
1 The effects of the angiotensin antagonists GR117289, losartan and Sar 1 Ala 8 ‐angiotensin II on the ex vivo binding of [ 125 I]‐Sar 1 Ile 8 ‐angiotensin II to rat liver and cortex/hippocampus (Cx/H) membranes have been investigated. 2 GR117289 (0.1–30 mg kg −1 , s.c., 2 h pretreatment) caused a dose‐dependent reduction in [ 125 I]‐Sar 1 Ile 8 ‐angiotensin II binding to both liver and cortex/hippocampus membranes. 3 Administration of a submaximal dose of GR117289 (1 mg kg −1 , s.c.) indicated that the peak inhibition of binding in the liver occurred within 0.5 h, whereas the peak inhibition of binding in the Cx/H occurred 2 h after drug treatment. 4 The effect of GR117289 was long lasting. Binding was still reduced in the Cx/H 48 h after drug treatment (10 mg kg −1 , s.c.) but had returned to normal 72 h after drug treatment. In the liver binding was still reduced 72 h after treatment with the same dose. 5 Losartan (1 − 30 mg kg −1 , s.c.) was equipotent with GR117289 in its ability to reduce liver binding, but was less effective at inhibiting binding to central receptors. 6 The non‐peptide antagonist Sar 1 Ala 8 ‐angiotensin II (3 and 10 mg kg −1 ) reduced binding in the liver but not in the Cx/H membranes. 7 These results suggest that, unlike the peptide antagonist Sar 1 Ala 8 ‐angiotensin II, the non‐peptide angiotensin antagonists, GR117289 and losartan, are able to cross the blood brain barrier and occupy central angiotensin II receptors.