This application is focussed on the signal transduction of dopamine. Recently, the applicant and several other investigators have demonstrated that some actions of dopamine in the brain may be mediated through the phosphoinositide signaling cascade rather than the classic adenylyl cyclase system. The goal of the proposed project will be to elucidate the mode and mechanisms of functional regulation in the phospholipase C coupled dopamine system. There are three primary questions to be addressed by the experiments: (1) Where in the brain does dopamine signal through the phospholipase C pathway?; (2) Which G-proteins mediate dopamine receptor coupling to phospholipase C?, and (3) How is the efficacy of dopamine receptor coupling to phospholipase C regulated?
| Panchalingam, S; Undie, A S (2001) SKF83959 exhibits biochemical agonism by stimulating [(35)S]GTP gamma S binding and phosphoinositide hydrolysis in rat and monkey brain. Neuropharmacology 40:826-37 |
| Undie, A S; Berki, A C; Beardsley, K (2000) Dopaminergic behaviors and signal transduction mediated through adenylate cyclase and phospholipase C pathways. Neuropharmacology 39:75-87 |
| Panchalingam, S; Undie, A S (2000) Optimized binding of [35S]GTPgammaS to Gq-like proteins stimulated with dopamine D1-like receptor agonists. Neurochem Res 25:759-67 |
| Undie, A S (1999) Relationship between dopamine agonist stimulation of inositol phosphate formation and cytidine diphosphate-diacylglycerol accumulation in brain slices. Brain Res 816:286-94 |
