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

Kevin L. Grove, Robert C. Speth

    Research output: Contribution to journalArticle

    17 Scopus citations

    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

    ASJC Scopus subject areas

    • Biochemistry
    • Pharmacology

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