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Assessment of glutamine synthetase activity by [ 13 N]ammonia uptake in living rat brain
Author(s) -
Momosaki Sotaro,
Ito Miwa,
Tonomura Misato,
Abe Kohji
Publication year - 2015
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.21781
Subject(s) - glutamine synthetase , glutamine , chemistry , ammonia , glutamate receptor , striatum , cerebral blood flow , biochemistry , medicine , endocrinology , biology , dopamine , amino acid , receptor
Glutamine synthetase (GS) plays an important role in glutamate neurotransmission or neurological disorder in the brain. [ 13 N]Ammonia blood flow tracer has been reported to be metabolically trapped in the brain via the glutamate‐glutamine pathway. The present study investigated the effect of an inhibitor of GS on [ 13 N]ammonia uptake in order to clarify the feasibility of measuring GS activity in the living brain. l ‐Methionine sulfoximine (MSO), a selective GS inhibitor was microinjected into the ipsilateral striatum in rats. [ 13 N]Ammonia uptake was quantified by autoradiography method as well as small animal positron emission tomography (PET) scans. The GS activity of the brain homogenate was assayed from the γ‐glutamyl transferase reaction. Autoradiograms showed a decrease of [ 13 N]ammonia radioactivity on the MSO‐injected side compared with the saline‐injected side of the striatum. This reduction could be detected with a small animal PET scanner. MSO had no effect on cerebral blood flow measured by uptake of [ 15 O]H 2 O. The reduction of [ 13 N]ammonia uptake was closely related to the results of GS activity assay. These results indicated that [ 13 N]ammonia may enable measurement of GS activity in the living brain. Synapse 69:26–32, 2015 . © 2014 Wiley Periodicals, Inc.