Abstract
Signal transduction for the characteristic long-term desensitization of glutamate receptors in Purkinje cells was investigated with wedge recordings from rat cerebellar slices. Long-term desensitization was induced specifically in the AMPA-selective subtype of glutamate receptors following brief exposure to 100 microM quisqualate. It was abolished either by treatment of the rat with pertussis toxin or by perfusion of a slice with BAPTA-AM, L-NMMA, hemoglobin, or inhibitor of PKG. Brief application of AMPA alone did not cause desensitization, but in combination with t-ACPD, sodium nitroprusside, or 8-bromo-cGMP, AMPA produced desensitization similar to that induced by quisqualate. These results indicate that the desensitization arises from activation of AMPA receptors in association with activation of metabotropic glutamate receptors, the latter leading to Ca2+ elevation to nitric oxide (NO) production to cGMP synthesis, and eventually to activation of PKG.
MeSH terms
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8-Bromo Cyclic Adenosine Monophosphate / pharmacology
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Animals
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Arginine / analogs & derivatives
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Arginine / pharmacology
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Cerebellum / drug effects
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Cerebellum / physiology
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Cyclic GMP / pharmacology
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Egtazic Acid / analogs & derivatives
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Egtazic Acid / pharmacology
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Ibotenic Acid / analogs & derivatives
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Ibotenic Acid / pharmacology
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In Vitro Techniques
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Perfusion
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Pertussis Toxin
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Purkinje Cells / drug effects*
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Quisqualic Acid / pharmacology
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Rats
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Rats, Inbred Strains
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Receptors, Glutamate
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Receptors, Neurotransmitter / drug effects*
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Signal Transduction / drug effects*
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Virulence Factors, Bordetella / pharmacology
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
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omega-N-Methylarginine
Substances
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Receptors, Glutamate
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Receptors, Neurotransmitter
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Virulence Factors, Bordetella
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1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester
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8-Bromo Cyclic Adenosine Monophosphate
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Ibotenic Acid
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omega-N-Methylarginine
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Egtazic Acid
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alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid
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Quisqualic Acid
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Arginine
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Pertussis Toxin
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Cyclic GMP