Abstract
Atrial natriuretic factor (ANF), a peptide hormone recently isolated from heart atria, appears to play an important role in the regulation of extracellular fluid volume and blood pressure. Indeed, natural and synthetic ANF rapidly and markedly stimulate natriuresis and diuresis and produce smooth muscle relaxation. Consistent with the hypothesis that ANF is a novel hormone, it was recently shown that ANF is present in circulation, and high affinity membrane receptors specific for ANF have been described in renal, vascular, and adrenal tissues. These important biological activities suggest that conditions like hypertension could be associated with defective ANF gene expression. We and others have shown by cDNA cloning that ANF is part of a larger precursor, pro-natriodilatin (PND). We now describe the isolation and structural analysis of the rat PND gene. Southern blot analysis of rat genomic DNA suggests the presence of a single PND gene per haploid genome. The PND coding sequences are interrupted by two short introns. A long alternating purine-pyrimidine tract (GT)9GATG(GT)27 is found 111 base pairs downstream of the polyadenylation site; such sequences could adopt Z-DNA configuration and they have been associated with sequences that appear very active in intergenic recombination. Comparison of the rat and human PND genomic sequences shows highest homology in 5'-flanking as well as in coding sequences. The rat PND gene will be a useful model to study the physiology and pathology of this important regulator of the cardiovascular system.
Highlights
From the $Laboratoire de Biologie Mokculaire des Eucaryotes, Znstitut de Recherches Cliniquesde Montreal, 110 Ouest, Avenuedes Pins, Montreal, Canada HZW lR7 and the $Department of Biochemistry, Queen’s University, Kingston, Canada K7L 3N6
The finding of potent natriureticd, iuretic, and vasorelaxant peptides inheartatriaopens a new and potentially very important field of investigation for theunderstanding of cardiovascular homeostasis in health and disease [1, 2].The structure of these recently isolated peptides was determined [3,4,5,6,7,8]andsyntheticatrialnatriuretic factor (ANF1)s-33is equipotentwith thenatural peptide [3].Antibodies raised against synthetic Atrial natriuretic factor (ANF) were used 1)to prove by immunocy
Molecular cloning and sequencing of rat [18,19,20,21,22,23]and human [18,24, 25] ANF encoding cDNAs revealed that ANFis present at the carboxyl end of a larger precursor molecule, pro-natriodilatin (PND), elsewhere referred toas proANF [20,21,22,23]or procardionatrin [19].We report the isolation and complete structure of the rat pro-natriodilatin gene
Summary
Stephania Argentin$, Mona Nemer$, Jacques DrouinS, Gary K. Consistent with the hypothesis that ANF is a novel hormone,it wasrecently shown that ANF is present in circulation, and high affinity membranereceptors specific for ANF have been described in renal, vascular, and adrenal tissues These important biological activities suggest that conditions like hypertension could be associated with defectiveANF gene expression. Molecular cloning and sequencing of rat [18,19,20,21,22,23]and human [18,24, 25] ANF encoding cDNAs revealed that ANFis present at the carboxyl end of a larger precursor molecule, pro-natriodilatin (PND), elsewhere referred toas proANF [20,21,22,23]or procardionatrin [19].We report the isolation and complete structure of the rat pro-natriodilatin (rPND) gene
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