Prouroguanylin’s role in the homeostatic response to dietary sodium: hormone precursor or active signaling agent? Public Deposited

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  • March 21, 2019
Creator
  • Fellner, Robert C.
    • Affiliation: School of Medicine, Department of Cell and Molecular Physiology
Abstract
  • High blood pressure affects more than 70 million Americans, putting them at a much greater risk for heart disease or a stroke. Sodium (Na+) is a major determinant of blood osmolarity and volume, and therefore plays a critical role in blood pressure regulation. Prouroguanylin (proUgn) has been implicated as a signal being sent from the small intestine to the kidney, in response to oral Na+ intake, that intestinal Na+ adsorption is eminent and renal Na+ excretion is necessary to maintain homeostasis. This concept, known as post-prandial natriuresis, is based on past observations of a faster natriuretic response from an oral salt load than from an equimolar intravenous infusion of NaCl. This role for proUgn is contentious however, as it has not been clearly shown if the role played by proUgn is that of a primary messenger from the intestine to the kidney in response to salt, if it is a intrarenal paracrine mechanism secondary to some other extrarenal signal in response to oral Na+ or even if it is proUgn itself or one of its' metabolites that are acting in the kidney. My studies address identification and quantification of proUgn and Ugn in relevant tissue compartments and additionally, I look at the effects of dietary Na+ on changes in the expression of proUgn and Ugn in these tissues. A novel adaptation of a binding assay technique allowed for urinary Ugn measurements that were found to directly correlate with dietary Na+ intake on a time scale that the prior techniques were insufficiently sensitive to achieve. Enteric and plasma proUgn do not change in response to dietary Na+, however a renal proUgn expression and Ugn in the urine do. Changes in plasma proUgn elicit a greater natriuretic response with a lower urinary Ugn concentration than urinary Ugn concentrations from infusions of Ugn in the blood. My conclusion is that proUgn is a secondary agent involved in volume and Na+ homeostasis, acting though some as yet unidentified renal metabolite/receptor mechanism. Further studies should focus on if there is another active cleavage product of proUgn and what receptor it (proUgn or Ugn) acts through.
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  • "... in partial fulfillment of the requirements for the degree of Doctor of Philosophy in the Department of Cell and Molecular Physiology – School of Medicine."
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  • Goy, Michael F.
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  • Chapel Hill, NC
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  • Open access
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