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γ‐VINYL GABA: EFFECTS OF CHRONIC ADMINISTRATION ON THE METABOLISM OF GABA AND OTHER AMINO COMPOUNDS IN RAT BRAIN
Author(s) -
Perry Thomas L.,
Kish Stephen J.,
Hansen Shirley
Publication year - 1979
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1979.tb02274.x
Subject(s) - hypotaurine , glutamate decarboxylase , glutamine , taurine , chemistry , amino acid , gaba transaminase , aminooxyacetic acid , medicine , metabolism , threonine , endocrinology , enzyme , biochemistry , pharmacology , biology , serine
Rats were given γ‐vinyl GABA (4‐amino‐hex‐5‐enoic acid), a new irreversible inhibitor of GABA aminotransferase (GABA‐T), by daily subcutaneous injection (100mgkg) for 11 days. Amino acids were quantitated in the brains of the γ‐vinyl GABA‐treated and control animals 24 h after the last injection, and enzyme activities of GABA‐T and glutamic acid decarboxylase (GAD) were measured. Chronic administration of γ‐vinyl GABA produced a 150% increase in brain GABA content, along with marked increases in the contents of B‐alanine and homocarnosine. Brain GABA‐T activity was reduced by 26%, and GAD activity was reduced by 22%. In addition, γ‐vinyl GABA caused a marked increase in hypotaurine content in rat brain, suggesting that it acts as an inhibitor of hypotaurine dehydrogenase, and it produced significant decreases in brain contents of glutamine and threonine. Although it is an effective GABA‐T inhibitor, γ‐vinyl GABA apparently affects several other brain enzymes as well, and it may not be an ideal drug for elevating brain GABA levels in man.