Central angiotensin IV binding sites: Distribution and specificity in guinea pig brain

A. V. Miller-Wing, J. M. Hanesworth, M. F. Sardinia, K. L. Hall, J. W. Wright, R. C. Speth, K. L. Grove, J. W. Harding

    Research output: Contribution to journalArticle

    93 Scopus citations

    Abstract

    Our laboratory has reported previously that a unique binding site specific for the hexapeptide angiotensin (A)II(3-8), now referred to as AIV, is present in a number of tissues including bovine adrenal gland, rabbit and guinea pig heart and guinea pig kidney, liver, lung, uterus and brain. The present results extend previous findings in the guinea pig brain and identify binding sites for AIV in the neocortex, paleocortex, hippocampus, medial habenula, superior and inferior colliculi, caudate putamen, thalamus, dorsal tegmentum, central gray, red nucleus, inferior olivary, oculomotor and hypoglossal nuclei and cerebellum. Binding of [125I]AIV in selected regions was shown to be of high affinity (K(d) = 0.60-1.47 nM), saturable (maximal number of binding sites = 181-449 fmol/mg of protein) and specific. This binding site was shown to be distinct from the AT1 and AT2 sites with K(i) values > 10-4 M for DuP 753, CGP42112A and PD123177. Changes at the N- terminal of the peptide, either by removal of the valine or by extension of the peptide, resulted in a large decrease in binding affinity. In contrast, C-terminal extensions resulted in little change in affinity for the binding site. Guanosine 5'-O-(3-thiotriphosphate) was shown to have no effect on binding, suggesting that the guinea pig brain binding site is not G-protein- linked. Potential functions associated with this newly discovered A binding site are discussed.

    Original languageEnglish (US)
    Pages (from-to)1718-1726
    Number of pages9
    JournalJournal of Pharmacology and Experimental Therapeutics
    Volume266
    Issue number3
    StatePublished - Dec 1 1993

    ASJC Scopus subject areas

    • Molecular Medicine
    • Pharmacology

    Fingerprint Dive into the research topics of 'Central angiotensin IV binding sites: Distribution and specificity in guinea pig brain'. Together they form a unique fingerprint.

  • Cite this

    Miller-Wing, A. V., Hanesworth, J. M., Sardinia, M. F., Hall, K. L., Wright, J. W., Speth, R. C., Grove, K. L., & Harding, J. W. (1993). Central angiotensin IV binding sites: Distribution and specificity in guinea pig brain. Journal of Pharmacology and Experimental Therapeutics, 266(3), 1718-1726.