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.
| Wang, C; Kuzma, M; Qiu, G et al. (2003) Heterogenous and compartment-specific activation of nonlymphocytic, mononuclear cells in intraabdominal sepsis. Exp Lung Res 29:503-21 |
| Qiu, Gang; Gribbin, Elizabeth; Harrison, Kathryn et al. (2003) Inhibition of gamma interferon decreases bacterial load in peritonitis by accelerating peritoneal fibrin deposition and tissue repair. Infect Immun 71:2766-74 |
| Qiu, G; Wang, C; Smith, R et al. (2001) Role of IFN-gamma in bacterial containment in a model of intra-abdominal sepsis. Shock 16:425-9 |
| Yin, K; Hock, C E; Lai, P S et al. (1999) Role of interferon-gamma in lung inflammation following cecal ligation and puncture in rats. Shock 12:215-21 |
