Glangliosides, sialylated glycosphingolipids are present in hihest concentration in neuronal membranes. Their functional roles are still poorly understood though it is known that they are implicated in neurotransmission since they modulate Na/K-ATPase activity and the electric responses in certain brain regions and that their abnormal accumulation in gangliosidoses results in severe neurologic disorsders and changes in the storage ans metabolism of some neurotransmitters. Little is known on their role in signal transduction systems coupled to neurotransmitter receptors and the only reported data describe the ability of gangliosides to stimulate basal adenilate ciclase activity, to inhibit proteine kinase C and to enhance diacilglicerol formation in brain membranes. To investigate this point in the present project we will study the effect of changes of ganglioside concentration in rat brain membranes on phosphoinosidite hydrolysis and adenilate ciclase activity, both basal and stimulated by guanine nucleotides and agoniosts. This study will include the characterization of the effects of individual gangliosides and the identification of the protein component of the transducing system (receptor, G-protein or efector enzyme) modulated by gangliosides
|Effective start/end date||1/04/91 → 31/03/92|
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