Heart Failure Specialized Center of Research (SCOR) is a multidisciplinary, interdepartmental clinical and basic research program that is directed at the reduction of death and disability from congestive heart failure. This proposed research program uses state of the art molecular biological techniques to address clinical, pharmacological and physiological questions relevant to the management of heart failure patients. The clinical component of this application encompasses research into the pathophysiology of exercise intolerance in ambulatory patients with congestive heart failure. The fundamental component encompasses research into the most fundamental biological processes by the mechanism by which calmodulation overexpression causes cardiac myocyte hypertrophy and hyperplasia; the mechanisms underlying the activation and desensitization of alpha- adrenergic receptors; the mechanisms underlying adenosine receptor mediated transmembrane signalling in vascular smooth muscle cells; and the mechanism of gating and drug binding to a transient outward potassium channel that plays an important role in cardiac repolarization. This integrated effort is aimed at translating the results of the applicant's diverse research efforts concerning the pathophysiology, clinical, pharmacologic and surgical therapy into the clinic to reduce death and disability from congestive heart failure.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Specialized Center (P50)
Project #
5P50HL054314-05
Application #
2857853
Study Section
Special Emphasis Panel (ZHL1-CSR-J (S1))
Project Start
1995-02-01
Project End
2000-12-31
Budget Start
1999-01-01
Budget End
2000-12-31
Support Year
5
Fiscal Year
1999
Total Cost
Indirect Cost
Name
Duke University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
071723621
City
Durham
State
NC
Country
United States
Zip Code
27705
Dun, N J; Le Dun, S; Chen, C T et al. (2000) Orexins: a role in medullary sympathetic outflow. Regul Pept 96:65-70
Palmer, T M; Stiles, G L (2000) Identification of threonine residues controlling the agonist-dependent phosphorylation and desensitization of the rat A(3) adenosine receptor. Mol Pharmacol 57:539-45
Palmer, T M; Stiles, G L (1999) Stimulation of A(2A) adenosine receptor phosphorylation by protein kinase C activation: evidence for regulation by multiple protein kinase C isoforms. Biochemistry 38:14833-42
Brahmajothi, M V; Campbell, D L; Rasmusson, R L et al. (1999) Distinct transient outward potassium current (Ito) phenotypes and distribution of fast-inactivating potassium channel alpha subunits in ferret left ventricular myocytes. J Gen Physiol 113:581-600
Ren, H; Stiles, G L (1999) Dexamethasone stimulates human A1 adenosine receptor (A1AR) gene expression through multiple regulatory sites in promoter B. Mol Pharmacol 55:309-16
Ren, H; Stiles, G L (1998) A single-stranded DNA binding site in the human A1 adenosine receptor gene promoter. Mol Pharmacol 53:43-51
Rasmusson, R L; Wang, S; Castellino, R C et al. (1997) The beta subunit, Kv beta 1.2, acts as a rapid open channel blocker of NH2-terminal deleted Kv1.4 alpha-subunits. Adv Exp Med Biol 430:29-37
Olah, M E (1997) Identification of A2a adenosine receptor domains involved in selective coupling to Gs. Analysis of chimeric A1/A2a adenosine receptors. J Biol Chem 272:337-44
Palmer, T M; Stiles, G L (1997) Identification of an A2a adenosine receptor domain specifically responsible for mediating short-term desensitization. Biochemistry 36:832-8
Rigolin, V H; Li, J S; Hanson, M W et al. (1997) Role of right ventricular and pulmonary functional abnormalities in limiting exercise capacity in adults with congenital heart disease. Am J Cardiol 80:315-22

Showing the most recent 10 out of 21 publications