The research proposed herein will investigate the cellular mechanisms which underlie the regulation of thermogenesis in hamster brown adipocytes. Thermogenesis in brown fat cells is subject to bimodal regulation: stimulation by catecholamines acting via both beta and alpha-1 adrenergic receptors and inhibition by adenosine, acting via A1 type receptors. Adenosine is capable of antagonizing the thermogenic response to both beta or alpha adrenergic receptors. The mechanisms underlying the thermogenic response to alpha adrenergic receptors are enigmatic as are the mechanisms underlying adenosine modulation of this response and the elucidation of both are long term objectives of this research project. The thermogenic response to activation of alpha-1 adrenergic receptors is associated with the activation of both phospholipase C and phospholipase A2 causing the breakdown of phosphoinositides and other membrane phospholipids and the accumulation of inositol phosphates, diacylglcerol and arachidonic acid. The present research seeks a more detailed understanding of alpha adrenergic regulation of phospholipid metabolism in these cells by studying phospholipase C and A2 activities in plasma membranes isolated from brown adipocytes. Subsequent experiments will investigate the mechanisms by which adenosine antagonizes the cellular responses to alpha-1 receptor activation. These experiments will test the hypothesis that adenosine acts by uncoupling alpha-1 receptors from either phospholipase C or phospholipase A2, and acts as an inhibitor of phosphoinositide breakdown and/or production of arachidonic acid in these cells. These studies will provide insight into the biochemical regulation of thermogenesis and will contribute information on the bimodal regulation of phospholipid metabolism in a unique cell type not previously investigated.
| Schimmel, R J (1989) Role of cell calcium in alpha-1 adrenergic receptor control of arachidonic acid release from brown adipocytes. Cell Signal 1:607-16 |
