Angiotensin II and non-angiotensin II displaceable binding sites for [3H]losartan in the rat liver

Kevin Grove, Robert C. Speth

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

By virtue of the more than 1000-fold selectivity of losartan (DuP 753) for the AT1 angiotensin II (AII) receptor subtype compared with the AT2 subtype, [3H]losartan may be a useful radioligand for studies of the AT1 receptor subtype. Comparison of Bmax values in the liver obtained from saturation isotherms using [3H]losartan (Bmax = 194 pmol g tissue) and [125I]sarcosine1,isoleucine8 angiotensin II (Bmax = 20 pmol g tissue) indicated that the AII receptor concentration was approximately 10% that of the [3H]losartan binding sites. In addition, AII at concentrations as high as 10 μM displaced less than one-third of specific [3H]losartan binding in the liver and less than 80% in the whole adrenal. The presence of non-AII displaceable [3H]losartan binding in the liver did not appear to result from metabolism of the radioligand since HPLC analysis of free and bound 3H revealed that greater than 90% of the 3H eluted at the same time as the parent [3H]losartan. This suggests that [3H]losartan binds with high affinity to a site(s) other than angiotensin II receptors in the rat liver.

Original languageEnglish (US)
Pages (from-to)1653-1660
Number of pages8
JournalBiochemical Pharmacology
Volume46
Issue number9
DOIs
StatePublished - Nov 2 1993
Externally publishedYes

Fingerprint

Losartan
Angiotensin II
Liver
Rats
Binding Sites
Angiotensin Receptors
Tissue
Metabolism
Isotherms
High Pressure Liquid Chromatography

ASJC Scopus subject areas

  • Pharmacology

Cite this

Angiotensin II and non-angiotensin II displaceable binding sites for [3H]losartan in the rat liver. / Grove, Kevin; Speth, Robert C.

In: Biochemical Pharmacology, Vol. 46, No. 9, 02.11.1993, p. 1653-1660.

Research output: Contribution to journalArticle

@article{b1adbd035a224e1e99010a03fd898cde,
title = "Angiotensin II and non-angiotensin II displaceable binding sites for [3H]losartan in the rat liver",
abstract = "By virtue of the more than 1000-fold selectivity of losartan (DuP 753) for the AT1 angiotensin II (AII) receptor subtype compared with the AT2 subtype, [3H]losartan may be a useful radioligand for studies of the AT1 receptor subtype. Comparison of Bmax values in the liver obtained from saturation isotherms using [3H]losartan (Bmax = 194 pmol g tissue) and [125I]sarcosine1,isoleucine8 angiotensin II (Bmax = 20 pmol g tissue) indicated that the AII receptor concentration was approximately 10{\%} that of the [3H]losartan binding sites. In addition, AII at concentrations as high as 10 μM displaced less than one-third of specific [3H]losartan binding in the liver and less than 80{\%} in the whole adrenal. The presence of non-AII displaceable [3H]losartan binding in the liver did not appear to result from metabolism of the radioligand since HPLC analysis of free and bound 3H revealed that greater than 90{\%} of the 3H eluted at the same time as the parent [3H]losartan. This suggests that [3H]losartan binds with high affinity to a site(s) other than angiotensin II receptors in the rat liver.",
author = "Kevin Grove and Speth, {Robert C.}",
year = "1993",
month = "11",
day = "2",
doi = "10.1016/0006-2952(93)90335-T",
language = "English (US)",
volume = "46",
pages = "1653--1660",
journal = "Biochemical Pharmacology",
issn = "0006-2952",
publisher = "Elsevier Inc.",
number = "9",

}

TY - JOUR

T1 - Angiotensin II and non-angiotensin II displaceable binding sites for [3H]losartan in the rat liver

AU - Grove, Kevin

AU - Speth, Robert C.

PY - 1993/11/2

Y1 - 1993/11/2

N2 - By virtue of the more than 1000-fold selectivity of losartan (DuP 753) for the AT1 angiotensin II (AII) receptor subtype compared with the AT2 subtype, [3H]losartan may be a useful radioligand for studies of the AT1 receptor subtype. Comparison of Bmax values in the liver obtained from saturation isotherms using [3H]losartan (Bmax = 194 pmol g tissue) and [125I]sarcosine1,isoleucine8 angiotensin II (Bmax = 20 pmol g tissue) indicated that the AII receptor concentration was approximately 10% that of the [3H]losartan binding sites. In addition, AII at concentrations as high as 10 μM displaced less than one-third of specific [3H]losartan binding in the liver and less than 80% in the whole adrenal. The presence of non-AII displaceable [3H]losartan binding in the liver did not appear to result from metabolism of the radioligand since HPLC analysis of free and bound 3H revealed that greater than 90% of the 3H eluted at the same time as the parent [3H]losartan. This suggests that [3H]losartan binds with high affinity to a site(s) other than angiotensin II receptors in the rat liver.

AB - By virtue of the more than 1000-fold selectivity of losartan (DuP 753) for the AT1 angiotensin II (AII) receptor subtype compared with the AT2 subtype, [3H]losartan may be a useful radioligand for studies of the AT1 receptor subtype. Comparison of Bmax values in the liver obtained from saturation isotherms using [3H]losartan (Bmax = 194 pmol g tissue) and [125I]sarcosine1,isoleucine8 angiotensin II (Bmax = 20 pmol g tissue) indicated that the AII receptor concentration was approximately 10% that of the [3H]losartan binding sites. In addition, AII at concentrations as high as 10 μM displaced less than one-third of specific [3H]losartan binding in the liver and less than 80% in the whole adrenal. The presence of non-AII displaceable [3H]losartan binding in the liver did not appear to result from metabolism of the radioligand since HPLC analysis of free and bound 3H revealed that greater than 90% of the 3H eluted at the same time as the parent [3H]losartan. This suggests that [3H]losartan binds with high affinity to a site(s) other than angiotensin II receptors in the rat liver.

UR - http://www.scopus.com/inward/record.url?scp=0027425551&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0027425551&partnerID=8YFLogxK

U2 - 10.1016/0006-2952(93)90335-T

DO - 10.1016/0006-2952(93)90335-T

M3 - Article

C2 - 8240422

AN - SCOPUS:0027425551

VL - 46

SP - 1653

EP - 1660

JO - Biochemical Pharmacology

JF - Biochemical Pharmacology

SN - 0006-2952

IS - 9

ER -