The objective of the proposed research is to elucidate the functional interaction of specific guanine nucleotide binding (G) proteins with adrenergic and muscarinic receptors in developing rat heart cells. The G protein composition of the neonatal rat heart differs significantly from that of the adult rat heart. A major part of the proposed work is therefore designed to determine if alterations in the G proteins are associated with alterations in the coupling of G proteins to the adrenergic and muscarinic receptors. Investigations toward this goal will be carried out using isolated cardiac myocytes obtained from rats at three different ages. These models will provide membranes containing varying amounts of G proteins. This information, along with antibodies to the G protein a subunits, will provide a first step toward the long-term objective of elucidating the regulation of expression and function of G proteins, which are vital for transmembrane signaling and modulation of cardiac function.
The specific aims of the proposed studies are to: 1) identify the G proteins which interact with the adrenergic and muscarinic receptors in neonatal heart cells using a combination of affinity chromatography and immunodetection; and 2) determine the role of receptor activation in regulating the abundance of G proteins in neonatal heart cells. An understanding of the biochemical mechanisms involved in neuro-hormonal control of the heart lays the groundwork for improved design of drugs for use in various cardiac problems, including arrhythmias, hypertrophy, and congestive heart failure.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Academic Research Enhancement Awards (AREA) (R15)
Project #
3R15HL058172-01S1
Application #
2743852
Study Section
Pharmacology A Study Section (PHRA)
Project Start
1997-09-30
Project End
2001-09-29
Budget Start
1997-09-30
Budget End
2001-09-29
Support Year
1
Fiscal Year
1998
Total Cost
Indirect Cost
Name
University of Medicine & Dentistry of NJ
Department
Anatomy/Cell Biology
Type
Schools of Osteopathy
DUNS #
City
Stratford
State
NJ
Country
United States
Zip Code
08084