title: Assessment of glutamine synthetase activity by [13N]ammonia uptake in living rat brain.
abstract: 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]H2 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.
authors.affiliation: Department of Drug Metabolism & Pharmacokinetics, Research Laboratory for Development, Shionogi & Co., Ltd., Futaba-cho, Toyonaka, Osaka, 561-0825, Japan.
authors.forename: Sotaro
authors.initials: S
authors.lastname: Momosaki
authors.forename: Miwa
authors.initials: M
authors.lastname: Ito
authors.forename: Misato
authors.initials: M
authors.lastname: Tonomura
authors.forename: Kohji
authors.initials: K
authors.lastname: Abe
mesh_terms: D000641:Ammonia; D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000000981:diagnostic imaging* / Q000187:drug effects / Q000201:enzymology*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005240:Feasibility Studies; D005974:Glutamate-Ammonia Ligase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008297:Male; D008717:Methionine Sulfoximine / Q000494:pharmacology; D009590:Nitrogen Radioisotopes; D010104:Oxygen Radioisotopes; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D017207:Rats, Sprague-Dawley; D014057:Tomography, X-Ray Computed; D014867:Water; D005723:gamma-Glutamyltransferase / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D009590:Nitrogen Radioisotopes; D010104:Oxygen Radioisotopes; D019275:Radiopharmaceuticals; D014867:Water; D008717:Methionine Sulfoximine; D000641:Ammonia; D005723:gamma-Glutamyltransferase; D005974:Glutamate-Ammonia Ligase
keywords: ammonia; glutamine synthetase; in vivo; positron emission tomography