DEPOLARIZING ACTIONS OF γ‐AMINOBUTYRIC ACID AND RELATED COMPOUNDS ON RAT SUPERIOR CERVICAL GANGLIA IN VITRO

Abstract

1Potential changes in rat superior cervical ganglia were recorded in vitro with surface electrodes.2 y-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 ED50 of 12.5 ,iM.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), 'y-amino-f3-hydroxybutyric acid (0.27), ,B-guanidino-propionic acid (0.12), guanidinoacetic acid (0.057), 6-aminovaleric acid (0.048),,-alanine (0.01), 2,4-diaminobutyric acid, 'y-guanidinobutyric acid, taurine and N-methyl-GABA (all <0.01). The folfowing compounds did not depolarize the ganglion at 10 mM concentrations: ai-and ,B-amino-n-butyric acids, a-amino-isobutyric 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 (IC50, 14 gM) and picrotoxin (IC50, 37 gM). Strychnine (IC50, 73 ,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.

γ‐AMINOBUTYRIC ACID AGONISTS: AN in vitro COMPARISON BETWEEN DEPRESSION OF SPINAL SYNAPTIC ACTIVITY AND DEPOLARIZATION OF SPINAL ROOT FIBRES IN THE RAT

“…The fibre receptors present on spinal roots (Evans, 1980) which are characterized by Table 1 are probably identical to the receptors which occur on unmyelinated peripheral nerve fibres (Brown & Marsh, 1978) because the relative potencies of GABA, 3-APS, GABOB and (3-guanidinopropionic acid (Bowery & Brown, 1974), isoguvacine, muscimol (Bowery, Collins, Hudson & Neal, 1978) for depolarization of sympathetic ganglia agree closely with the values of Table 1. A comparison is given in Figure 3, between relative values for displacement of GABA binding to rat brain membranes (Johnston et al, 1978b) and the present relative potencies of the compounds listed in Table 1. A positive correlation (correlation coefficient 0.90, P < 0.001), was observed between displacement of GABA binding and fibre depolarizing potencies (Table 1) …”

THE ACTION OF ACETYLCHOLINE ANTAGONISTS ON AMINO ACID RESPONSES IN THE FROG SPINAL CORD in vitro

“…Indeed, the observation that curare blocks both cortical inhibition and the action of y-aminobutyric acid (GABA) (Hill, Simmonds & Straughan, 1972) supports this notion. Furthermore, the observation that picrotoxin, bicuculline (DeGroat, 1970;Bowery & Brown, 1974) and strychnine (Alving, 1961;Philis & York, 1967;Kehoe, 1972;Faber & Klee, 1974;Bowery & Brown, 1974) can antagonize responses to acetylcholine, at least in high concentrations, indicates that acetylcholine and neutral amino acid responses have features in common. Thus, the present study was undertaken to examine the effects of a number of acetylcholine antagonists on amino acid responses in the frog isolated spinal cord.…”

Pharmacological evidence for the possible involvement of repetitive action potentials in facilitation by GABA of catecholamine secretion in bovine adrenal chromaffin cells

“…There is much evidence from electrophysiological studies to show that GABA depolarizes the cell body of sympathetic ganglion via changes in Cl-permeability (DeGroat, 1970;Bowery & Brown, 1974;Adams & Brown, 1975) and that chromaffin cells possess GABA-induced Cl-currents (Bormann & Clapham, 1985;Cottrell et al, 1985). Therefore, it may be assumed that GABA depolarizes chromaffin cells, resulting in an activation of voltage-sensitive ion channels and, as a consequence, a modulation of Ca2+ homeostasis influencing CA secretion.…”