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Transmembrane signaling through phospholipase C in human cortical membranes

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Abstract

Stimulation of phosphoinositide-specific phospholipase C (PLC) by carbachol, dopamine and serotonin was measured by supplying exogenous [3H]phosphatidylinositol 4,5-bisphosphate to membranes prepared from human cortex dissected and frozen at autopsy. Subjects with Alzheimer's disease, Parkinson's disease or schizophrenia were compared to age-matched controls with no known neurological disorders. Stimulation of PLC by the neurotransmitters was dependent on the presence of GTPγS. Carbachol elicited the greatest stimulations of PLC followed by serotonin and then dopamine. The maximal stimulations of PLC evoked by a neurotransmitter were similar for the various categories of subjects except in Parkinson's patients, where dopamine failed to stimulate PLC beyond the activity attained with carbachol. In the presence of carbachol, the sensitivity of PLC to GTPγS was significantly increased in Alzheimer's membranes, but not in age-matched controls or Parkinson's. Overall, the experiments demonstrate the feasibility for using the exogenous substrate assay to study the functionality of the phosphoinositide transmembrane signaling system in human brain.

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Abbreviations

PLC:

phospholipase C

GTPγS:

guanosine 3′-O-thiotriphosphate

Gpp(NH)p:

5′-guanylyl-imidodiphosphate

DA:

dopamine

CCh:

earbachol

5-HT:

serotonin

PIP2 :

phosphatidylinositol 4,5-bisphosphate

PIP:

phosphatidylinositol 4-bisphosphate

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  1. Enrique Claro

    Present address: Departamento de Bioquimica y Biologia Molecular Facultad de Medicina, Universidad Autonoma de Barcelona, 08193, Bellaterra, Barcelona, Spain

Authors and Affiliations

  1. Department of Biochemistry, University of Tennessee, Memphis, 858 Madison Avenue, 38163, Memphis, Tennessee

    Michael A. Wallace

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Wallace, M.A., Claro, E. Transmembrane signaling through phospholipase C in human cortical membranes. Neurochem Res 18, 139–145 (1993). https://doi.org/10.1007/BF01474676

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