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Effect of NG-nitro-L-arginine methyl ester a nitric oxide synthase inhibitor on neurotransmitter receptor systems in aged rats
Authors:Tsutomu Araki  Yoshiteru Oshima  Hiroyki Kato  Katsuro Shuto  Yasuto Itoyama
Institution:Department of Neurology Tohoku University School of Medicine, Sendai;Department of Pharmacognosy, Faculty of Pharmaceutical Sciences, Tohoku University, Sendai;Medicinal Research Group II, Kazusa Research Laboratories, Tokyo Tanabe Co. Ltd, Japan
Abstract:In order to examine the effect of age and nitric oxide synthase inhibitor NG-nitro-L-arginine methl ester (l -NAME) we studied the changes on major neurotransmitter receptor systems in 6 (adult and 24-month-old (aged) Fischer male rats using receptor autoradiography. l -name was administrated intraperitoneally in aged rats once a day for 4 weeks. 3H]QNB (quinuclidinyl benzilate) 3HC (hemicholinium-3) 3H] muscimol 3H] SCH 23390 (N-methyl-3H] N-methyl-3H]R+]-8-chloro-2 3 4 5-tetrahydro-3-methyl-5-phenyl-7-il-benzazepine) 3H] mazindol were used as markers of muscarinic acetylcholine receptors high-high-affinity choline uptake sites GABAA (γ-aminobutyric acid (SP2)A) receptors dopamine D1 receptors dopamine D2 receptors and dopamine uptake sites respectively. The age-related change in 3H muscimol binding in the brain was more pronounced than that in 3H] QNB 3H]HC 3H]SCH 23390 3H] nemonapride and 3H] nemonapride and 3H] mazindol binding.Chronic treatment (4 weeks) with l -NAME caused no significant changes in sp1)3H] muscimol 3H SCH 23390 and 3H] nemonapride binding in most areas of aged rat brain as compared with vehicle-treated aged animals. However chronic treatment with l -NAME caused a significant reduction in 3H] HC and 3H] mazindol binding in any brain regions of aged rats in comparison with the vehicle-treated aged animals. These results demonstrate that the GABAergic system is more susceptible to aging processes than cholinergic and dopaminergic systems in teh brain. Furthermore our findings suggest that nitric oxide may play some role in the regulation of choline uptake and dopamine uptake systems during aging processes.
Keywords:aging  nitric oxide synthase inhibitor  acetylcholine receptor  choline uptake sites  GABAA receptor  dopamine D1 receptor  dopamine D2 receptor  dopamine uptake sites  receptor autoradiography rat
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