Extrasynaptic effects of GABA (gamma-aminobutyric acid) agonists on myelinated axons of peripheral nerve.
Effects of the inhibitory neurotransmitter, GABA (gamma-aminobutyric acid) on the excitability of myelinated fibers of isolated amphibian sciatic nerves and their dorsal and ventral spinal roots have been compared with those of a GABAA agonist, THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol), and the GABAB agonist baclofen. Graded, prolonged increases in the amplitude of A-fiber half-maximal compound action potentials of Rana ballenderi sciatic nerves were evoked by GABA (Rmax = 49%, EC50 = 0.1 mM); responses to THIP were smaller (Rmax = 34%, EC50 = 1.1 mM) and with a different, distinctly biphasic recovery phase. In studies of Rana catesbeiana nerves and their attached spinal roots, excitability increases produced in fibers of the ventral roots by GABA were smaller than those of the dorsal roots. Peak changes evoked by THIP in both roots were similar to the effects of GABA on the ventral root; however, THIP's ventral root response showed much less sensitivity and was followed by a rapid recovery phase, undershoot, and secondary, prolonged enhancement. Bicuculline methiodide antagonized agonist-induced increases, and revealed the presence of significant decreases in excitability of the ventral root fibers at concentrations of GABA or THIP < 3 mM. Baclofen evoked inconsistent changes in the excitability of whole nerve and root fibers; small increases occurred with lower doses and secondary, delayed decreases with higher doses. The high concentration (> or = 0.1 mM) of the active isomer needed to cause a small response suggests a limited contribution and (or) presence of GABAB receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
Liske
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Department of Pharmacology, University of Toronto, ON, Canada.
Morris
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D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001369:Axons / Q000187:drug effects*; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000494:pharmacology; D018755:GABA Agonists / Q000494:pharmacology*; D018756:GABA Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D007555:Isoxazoles / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009046:Motor Neurons / Q000187:drug effects; D009413:Nerve Fibers, Myelinated / Q000187:drug effects*; D010525:Peripheral Nerves / Q000166:cytology* / Q000187:drug effects; D011892:Rana catesbeiana; D011898:Ranidae; D012584:Sciatic Nerve / Q000187:drug effects / Q000502:physiology; D013126:Spinal Nerve Roots / Q000187:drug effects / Q000502:physiology; D013569:Synapses / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D018755:GABA Agonists; D018756:GABA Antagonists; D007555:Isoxazoles; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; C015542:gaboxadol; D001640:Bicuculline