Regulation of Neurotransmitter Responses in the Central Nervous System.
Final rept. 11 May 85-31 Jul 86,
TEXAS UNIV MEDICAL SCHOOL AT HOUSTON
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The aim of this study was to characterize the mechanism whereby activation of gamma-aminobutyric acidB GABAB receptors augments modulates receptor-mediated second and alpha-adrenergic agonists to augment the cyclic AMP response to isoproterenol was greatly diminished in the presence of EGTA or quinacrine. Likewise, this response was attenuated in the brains of animals treated chronically with corticosterone. Moreover, it was discovered that phorbol esters augment the second messenger response in a manner similar to the GABAB and alpha-adrenergic agonists. Phosphorylation studies revealed that exposure of the brain tissue to phorbol esters leads to the phosphorylation of a constituent that resembles the inhibitory guanine nucleotide binding protein. These findings suggest that the modulation of brain neurotransmitter responses may be mediated by activation of phospholipase A2 andor protein kinase C, and that the critical factor in the modulatory response may be the phospharylation of a protein that regulates adenylate cyclase activity. Keywords Brain chemistry Cyclic AMP Neuromodulation.
- Anatomy and Physiology