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DEPOLARIZING ACTIONS OF γ‐AMINOBUTYRIC ACID AND RELATED COMPOUNDS ON RAT SUPERIOR CERVICAL GANGLIA IN VITRO
Author(s) -
BOWERY N.G.,
BROWN D.A.
Publication year - 1974
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1974.tb08563.x
Subject(s) - depolarization , strychnine , hexamethonium , carbachol , chemistry , bicuculline , taurine , reversal potential , picrotoxin , superior cervical ganglion , medicine , gamma aminobutyric acid , endocrinology , butyric acid , biophysics , glycine , amino acid , gabaa receptor , biochemistry , biology , receptor , patch clamp
1 Potential changes in rat superior cervical ganglia were recorded in vitro with surface electrodes. 2 γ‐aminobutyric acid (GABA) produced a transient, low‐amplitude ganglion depolarization at rest, and a transient hyperpolarization in ganglia depolarized by carbachol. Depolarization was not prevented by preganglionic denervation. The log dose‐response curve for depolarization was sigmoid with a mean ED 50 of 12.5 μ m . 3 The ganglion was depolarized in similar manner by the following compounds (mean molar potencies relative to GABA (=1) in brackets): 3‐aminopropane sulphonic acid (3.4), γ‐amino‐β‐hydroxybutyric acid (0.27), β‐guanidino‐propionic acid (0.12), guanidinoacetic acid (0.057), δ‐aminovaleric acid (0.048), β‐alanine (0.01), 2,4‐diaminobutyric acid, γ‐guanidinobutyric acid, taurine and N ‐methyl‐GABA (all <0.01). The following compounds did not depolarize the ganglion at 10 m m concentrations: α‐ and β‐amino‐ n ‐butyric acids, α‐amino‐ iso ‐butyric acid, glycine and glutamic acid. 4 Depolarization declined in the continued presence of GABA. Ganglia thus ‘desensitized’ to GABA showed a diminished response to other amino acids but not to carbachol. 5 The effect of GABA was not antagonized by hyoscine and hexamethonium in combination, in concentrations sufficient to block responses to carbachol. 6 Responses to GABA were blocked more readily than those to carbachol by bicuculline (IC 50 , 14 μ m ) and picrotoxin (IC 50 , 37 μ m ). Strychnine (IC 50 , 73 μ m ) was a relatively weak and less selective GABA‐antagonist. 7 It is concluded that sympathetic ganglion cells possess receptors for GABA and related amino acids which are (a) different from the acetylcholine receptors and (b) similar to GABA receptors in the central nervous system.