VASOACTIVE HORMONES: RECEPTORS AND SIGNALING MECHANISMS

  • Koop, Dennis (PI)
  • Chang, Chung- (PI)
  • Scarpa, Antonio (PI)
  • Thibonnier, Marc (PI)
  • Douglas, Janice (PI)
  • Hopfer, Ulrich (PI)

Project: Research project

Description

The long-term goal of this Program Project is to elucidate cellular and
molecular mechanisms whereby vasoactive hormones contribute to blood
pressure regulation. This approach necessitates a multidisciplinary
group encompassing disciplines of cell and organ physiology,
biochemistry, pharmacology, neuroscience and molecular biology which we
have assembled. The Program stresses a broad application to the problem
of receptor-effector coupling mechanisms employing human, animals, cells
and subcellular organelles and emphasized the application of state-of-
the-art technology. Studies at a molecular level include: a)
purification and sequencing of receptors and enzymes; b) development of
monoclonal antibodies and probes for in situ hybridization; c)
determination of regulatory role of GTP-binding proteins kinases and
phosphatases on transporters and key phospholipases involved in signal
transduction; d) use of transgenic models to simulate human disease and
investigate the potentiating role of lactogenic hormone on vascular
reactivity and steroid biosynthesis. Investigation at a cellular level
will employ fluorescent probes to explore signal transduction and
cellular transport in brain, kidney epithelium, vascular smooth muscle
and glomerular messangium. The projects can be broadly grouped into two
areas that investigate central and peripheral mechanisms of blood
pressure regulation. Those of relevance to peripheral sites of action
include: 1) Project 1 which assesses mechanisms of AII-induced signal
transduction in proximal tubular epithelium, the site of a novel class
of AII receptors; 2) Project 2 involves purification and regulation of
proximal tubular cytochrome P450 isozymes important to arachidonic acid
metabolism and epithelial electrolyte transport; Project 3 that involves
a detailed characterization of transport pathways in proximal tubular
epithelium; and Project 4 involves purification of V-1 vasopressin
receptor and assessment of the regulatory role in hypertension. Cores
provide administrative, tissue culture and state-of-the-art
instrumentation to enhance scientific merit of all projects.
StatusFinished
Effective start/end date7/1/894/30/06

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

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Arachidonic Acid
Cytochrome P-450 Enzyme System
Isoenzymes
Mixed Function Oxygenases
Rabbits
Acids
Ion Exchange
Phenobarbital
Microsomes
Epithelium
High Pressure Liquid Chromatography
Kidney
Enzymes

ASJC

  • Medicine(all)