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-AMINOBTJTYRIC ACID AND RELATED AMINO ACIDS ON MAMMALIAN AUTONOMIC GANGLIA
1 Department of Physiology, Australian National University, Canberra, Australia, Department of Pharmacology, University of Pennsylvania, Philadelphia, Pennsylvania and Department of Pharmacology, University of Pittsburgh, Pittsburgh, Pennsylvania
An electrophysiologic study was made of the effects of
-aminobutyric acid (GABA) and related amino acids on autonomic ganglia of the cat and rabbit. In the superior cervical ganglion of the cat the i.a. administration of GABA evoked a negative ganglionic surface potential and depressed nicotinic and muscarinic ganglionic transmission as well as the ganglionic responses to injected muscarinic stimulating agents. GABA exhibited similar depressant actions in other autonomic ganglia. These effects were antagonized by picrotoxin but were unaffected by strychnine, cholinergic blocking agents or chronic preganglionic denervation. Other amino acids including
-amino-
-hydroxybutyric acid, 3-amino-1-propanesulfonic acid and
-alanine mimicked many of the ganglionic effects of GABA; however, glycine, a potent depressant of spinal neurons, was inactive. The results indicate that amino acids react with receptor sites on ganglion cells to elicit a reduction in resting membrane potential and a depression of membrane excitability. The antagonism between picrotoxin and GABA in ganglia represents the first demonstration of this interaction in the mammalian nervous system and raises the possibility that a similar pharmacologic antagonism may yet be discovered at sites in the mammalian central nervous system.
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