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A membrane form of guanylate cyclase is an atrial natriuretic peptide receptor

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Abstract

ATRIAL natriuretic peptide (ANP) is a polypeptide hormone whose effects include the induction of diuresis, natriuresis and vasorelaxation1. One of the earliest events following binding of ANP to receptors on target cells is an increase in cyclic GMP concentration, indicating that this nucleotide might act as a mediator of the physiological effects of the hormone2,3. Guanylate cyclase exists in at least two different molecular forms: a soluble haem-containing enzyme consisting of two summits4,5 and a non-haem-containing transmembrane protein having a single subunit6. It is the membrane form of guanylate cyclase that is activated following binding of ANP to target cells3,7,8. We report here the isolation, sequence and expression of a complementary DNA clone encoding the membrane form of guanylate cyclase from rat brain. Transfec-tion of this cDNA into cultured mammalian cells results in expression of guanylate cyclase activity and ANP-binding activity. The ANP receptor/guanylate cyclase represents a new class of mammalian cell-surface receptors which contain an extracellular ligand-binding domain and an intracellular guanylate cyclase catalytic domain.

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Authors and Affiliations

  1. The Howard Hughes Medicaf Institute, Vanderbilt University School of Medicine, Nashville, Tennessee, 37232, USA

    Michael Chinkers, David L. Garbers & Stephanie Schulz

  2. Departments of Pharmacology, Vanderbilt University School of Medicine, Nashville, Tennessee, 37232, USA

    Michael Chinkers, David L. Garbers & Stephanie Schulz

  3. Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, 37232, USA

    David L. Garbers

  4. Department of Molecular Biology, Genentech Inc., 460 Point San Bruno Boulevard, South San Francisco, California, 94080, USA

    Ming-Shi Chang, David G. Lowe & David V. Goeddel

  5. Laboratory of Biochemical Genetics, National Institutes of Health, Bethesda, Maryland, 20892, USA

    Hemin Chin

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  1. Michael Chinkers
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  2. David L. Garbers
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  3. Ming-Shi Chang
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  4. David G. Lowe
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  5. Hemin Chin
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  6. David V. Goeddel
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  7. Stephanie Schulz
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Chinkers, M., Garbers, D., Chang, MS. et al. A membrane form of guanylate cyclase is an atrial natriuretic peptide receptor. Nature 338, 78–83 (1989). https://doi.org/10.1038/338078a0

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  • DOI: https://doi.org/10.1038/338078a0

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