Abstract
The cerebellar cells that account for glutamate-dependent cyclic GMP (cGMP) production, involving activation of the ionotropic glutamate receptors/nitric oxide synthase/soluble guanylyl cyclase pathway, are not fully established. In the present paper we have searched for the localisation of the cGMP response to the nitric oxide (NO) donor S-nitroso-penicillamine (SNAP 1muM), expected to generate local NO concentrations in the low nanomolar physiological range and evoking a cGMP response dependent on glutamate release and on the consequent activation of ionotropic glutamate NMDA/non-NMDA receptors, in cerebellar slices from adult rat. We have found that low concentration of exogenous NO evoked cGMP accumulation in Purkinje cells in an ionotropic glutamate receptor-dependent and tetrodotoxin-sensitive manner. Such immunocytochemical localisation appears consistent with functional evidence for physiologically relevant glutamate-dependent cGMP production in Purkinje cells in rat cerebellar cortex.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Astrocytes / cytology
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Astrocytes / metabolism
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Biomarkers / metabolism
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Calbindins
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Cerebellar Cortex / cytology
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Cerebellar Cortex / drug effects
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Cerebellar Cortex / metabolism*
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Cyclic GMP / biosynthesis*
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Excitatory Amino Acid Antagonists / pharmacology
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Glial Fibrillary Acidic Protein / metabolism
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Glutamic Acid / metabolism
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Guanylate Cyclase / metabolism
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Immunohistochemistry
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Male
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Nitric Oxide / metabolism*
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Nitric Oxide Donors / pharmacology
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Nitric Oxide Synthase Type I / metabolism
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Organ Culture Techniques
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Purkinje Cells / cytology
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Purkinje Cells / drug effects
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Purkinje Cells / metabolism*
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Rats
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Rats, Sprague-Dawley
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Receptors, Cytoplasmic and Nuclear / metabolism
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Receptors, Glutamate / drug effects
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Receptors, Glutamate / metabolism*
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Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors
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Receptors, N-Methyl-D-Aspartate / metabolism
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S100 Calcium Binding Protein G / metabolism
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Sodium Channel Blockers / pharmacology
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Soluble Guanylyl Cyclase
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
Substances
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Biomarkers
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Calbindins
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Excitatory Amino Acid Antagonists
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Glial Fibrillary Acidic Protein
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Nitric Oxide Donors
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Receptors, Cytoplasmic and Nuclear
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Receptors, Glutamate
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Receptors, N-Methyl-D-Aspartate
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S100 Calcium Binding Protein G
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Sodium Channel Blockers
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Nitric Oxide
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Glutamic Acid
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Nitric Oxide Synthase Type I
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Guanylate Cyclase
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Soluble Guanylyl Cyclase
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Cyclic GMP