Two types of well defined primary dissociated cell cultures from 7-9 day old rat cerebellum, one enriched in neurons (excitatory granule cells and inhibitiory stellate and basket cells) and the other containting glia (type I astrocytes) a specifically designed culture perfusion chamber, high performance liquid chromatography (HPLC), and biochemical techniques will be used to, 1) identify the pharmacological characteristics and cellular origins of stimulus-evoked and spontaneous release/efflux of the endogenous neurotransmitter and neuromodulatory substance aspartate, glutamate, adenosine, GABA and taurine. 2) investigate the roles of the signal transducing system, protein kinase C, Ca2+-calmodulin and inositol phospholipid metabolism which through ligand-receptor interactions may produce and regulate the release of endogenous aspartate, glutamate, adenosine, GABA and taurine. Contingent upon the accomplishment of these aims, it will perhaps then be possible to study the detailed pharmacology of in vitro CNS development, meaningfully test the in vitro effects of new drugs on cultured CNS cells, and examine the role of afferent input on cerebellar development in vitro. A detailed determination of the contributions of specific cell types to the composite pharmacology of the cerebellum is our major long-term goal.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS020632-05
Application #
3401113
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1984-12-01
Project End
1990-11-30
Budget Start
1988-12-01
Budget End
1989-11-30
Support Year
5
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Iowa
Department
Type
Schools of Medicine
DUNS #
041294109
City
Iowa City
State
IA
Country
United States
Zip Code
52242
Simmons, M L; Dutton, G R (1992) Neuronal origins of K(+)-evoked amino acid release from cerebellar cultures. J Neurosci Res 31:646-53
Dutton, G R; Rogers, K L (1992) Evoked endogenous taurine release from cultured cerebellar neurons. Adv Exp Med Biol 315:269-76
Moore, S A; Yoder, E; Murphy, S et al. (1991) Astrocytes, not neurons, produce docosahexaenoic acid (22:6 omega-3) and arachidonic acid (20:4 omega-6). J Neurochem 56:518-24
Albrecht, J; Simmons, M; Dutton, G R et al. (1991) Aluminum chloride stimulates the release of endogenous glutamate, taurine and adenosine from cultured rat cortical astrocytes. Neurosci Lett 127:105-7
Rogers, K L; Philibert, R A; Dutton, G R (1991) K(+)-stimulated amino acid release from cultured cerebellar neurons: comparison of static and dynamic stimulation paradigms. Neurochem Res 16:899-904
Dutton, G R; Barry, M; Simmons, M L et al. (1991) Astrocyte taurine. Ann N Y Acad Sci 633:489-500
Rogers, K L; Philibert, R A; Dutton, G R (1990) Glutamate receptor agonists cause efflux of endogenous neuroactive amino acids from cerebellar neurons in culture. Eur J Pharmacol 177:195-9
Tigges, G A; Philibert, R A; Dutton, G R (1990) K(+)- and temperature-evoked taurine efflux from hypothalamic astrocytes. Neurosci Lett 119:23-6
Philibert, R A; Rogers, K L; Dutton, G R (1989) K+-evoked taurine efflux from cerebellar astrocytes: on the roles of Ca2+ and Na+. Neurochem Res 14:43-8
Philibert, R A; Rogers, K L; Dutton, G R (1989) Stimulus-coupled taurine efflux from cerebellar neuronal cultures: on the roles of Ca++ and Na+. J Neurosci Res 22:167-71

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