Pharmacological evidence for a role of gamma-aminobutyric acid A receptor mechanism in modulating nitric oxide synthase activity in rat brain.
The role of gamma-aminobutyric acid (GABA) mechanism on the synthesis of nitric oxide (NO) has been investigated by measuring the activity of nitric oxide synthase (NOS) and the concentration of NO in rat brain 15 min after administration of anticonvulsant doses of diazepam (0.25 and 0.5 mg/kg) which is known to activate GABA A receptor for its anticonvulsant action. Diazepam enhanced both NOS activity and the concentration of NO in a dose-dependent manner. A reversal has been observed in animals treated with a convulsant dose of picrotoxin (5 mg/kg) which is known to produce convulsions by blocking GABA A receptor mechanism. These results suggest that a functional interaction occurs between GABA A receptor activity and NO synthesis in the brain.
Paul
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Department of Pharmacology and Environmental Toxicology, Dr. A.L.M. Postgraduate Institute of Basic Medical Sciences, University of Madras, Taramani, 600 113, Chennai, India.
Subramanian
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Rajasekaran
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K
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D003975:Diazepam / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018756:GABA Antagonists / Q000494:pharmacology; D018757:GABA Modulators / Q000494:pharmacology; D058787:GABA-A Receptor Antagonists; D008297:Male; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D010852:Picrotoxin / Q000494:pharmacology; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*
D003975:Diazepam; D018756:GABA Antagonists; D018757:GABA Modulators; D058787:GABA-A Receptor Antagonists; D019001:Nitric Oxide Synthase; D010852:Picrotoxin; D011963:Receptors, GABA-A