Pre- and Non-Synaptic Activities of GABA and Related Amino Acids in the Mammalian Nervous System

Curtis, D. R.

doi:10.1007/978-1-4613-4030-0_5

Cited by 19 publications

(6 citation statements)

References 146 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is possible that GABA released at axo-somatic contacts may 'wash-over' onto presynaptic sites in close proximity but a postsynaptic location seems more plausible. Thus, like bicuculline-sensitive GABA receptors, Curtis, 1978), GABAB sites may exist at pre-and postsynaptic sites depending on the brain region.…”

Section: Discussionmentioning

confidence: 99%

Characteristics of GABA_B receptor binding sites on rat whole brain synaptic membranes

Bowery

Hill

Hudson

1983

British J Pharmacology

391

116

View full text Add to dashboard Cite

Saturable binding of (±)‐[3H]‐baclofen and [3H]‐γ‐aminobutyric acid ([3H]‐GABA) to rat brain crude synaptic membranes has been examined by means of a centrifugation assay. The binding of [3H]‐baclofen could be detected in fresh or previously frozen tissue and was dependent on the presence of physiological concentrations of Ca2+ or Mg2+ although a lower affinity Na+‐dependent component could also be observed. Both components probably reflect binding to receptor recognition sites. The saturable portion of bound [3H]‐baclofen formed 20.3 ± 6.9% of total bound ligand. This could be displaced by GABA (IC50 =.0.04 μm), (−)‐baclofen (0.04 μm) and to a much lesser extent by (+)‐baclofen (33 μm). Isoguvacine, piperidine‐4‐sulphonic acid and bicuculline methobromide were inactive (up to 100 μm) and muscimol was only weakly active (IC50 = 12.3 μm). Saturable binding of [3H]‐GABA increased on adding CaCl2 or MgSO4 (up to 2.5 mm and 5.0 mm respectively) to the Tris‐HCl incubation solution. This binding (GABAB site binding) was additional to the bicuculline‐sensitive binding of GABA (GABAA site binding) and could be completely displaced by (−)‐baclofen (IC50 = 0.13 μm). Increasing the Ca2+ concentration (0 to 2.5 mm) increased the binding capacity of the membranes without changing their affinity for the ligand. The binding of [3H]‐GABA to GABAB sites could be demonstrated in fresh as well as previously frozen membranes with a doubling of the affinity being produced by freezing. Further incubation with the non‐ionic detergent Triton‐X‐100 (0.05% v/v) reduced the binding capacity by 50%. The pharmacological profile of displacers of [3H]‐GABA from GABAB sites correlated well with that for [3H]‐baclofen displacement. A correlation with data previously obtained in isolated preparations of rat atria and mouse vas deferens was also apparent. It is concluded that [3H]‐baclofen or [3H]‐GABA are both ligands for the same bicuculline‐insensitive, divalent cation‐dependent binding sites in the rat brain.

show abstract

Section: Discussionmentioning

confidence: 99%

Characteristics of GABA_B receptor binding sites on rat whole brain synaptic membranes

Bowery

Hill

Hudson

1983

British J Pharmacology

391

116

View full text Add to dashboard Cite

show abstract

“…However, there is also electrophysiolodcal eta, 1980) to coincide with the higher concentrations of evidence to show that baclofen has a highly specific GABA nerve terminals in laminae and In (Hunt et action on Postsynaptic neurones mediated by an inal., 1981) where axo-aonic as well as axo-somatic GA-crease in a voltage-dependent potassium conductance BAergic connections have been detected (Barber et a]., (Giihwiler and Brown, 1985;Inoue et al, 1985a;New-1978). These ao-axonic contacts are thought to be the be-and Nicoll, 19851, and the question therefore arises anatomical substrate for the presynaptic inhibitory role as to how the GABAB binding in the spinal of GABA at primary afferent terminals, and bicuculline-cord might be proportioned between pre-and postsynsensitive receptors are strongly implicated at these sites aptic sites and indeed contribute to the specific action of (Curtis, 1978).…”

Section: Introductionmentioning

confidence: 99%

The location of GABA_B receptor binding sites in mammalian spinal cord

Price

Kelly

Bowery

1987

Synapse

118

View full text Add to dashboard Cite

GABAB binding sites in rat spinal cord have been detected by receptor autoradiography using 3H-GABA in the presence of isoguvacine. The sites could be demonstrated throughout the spinal cord grey matter. The maximum concentration of GABAB sites occurred in lamina II with substantial amounts in other laminae of the dorsal horn. Much lower levels were detected in the ventral horn. Unilateral rhizotomy reduced the number of GABAB sites in the dorsal horn without affecting levels in the ventral horn. The greatest reduction occurred in lamina II with 18% loss 2 days after surgery, 23% after 4 days, 25% after 6 days, and 48% after 15 days. The change after 15 days was comparable to that produced 4 months after neonatal capsaicin administration (50 mg/kg). The only apparent difference between rhizotomy and capsaicin treatment occurred in lamina IV, where rhizotomy produced a greater reduction than capsaicin. 3H-Neurotensin binding in sections from the same animals was unaltered after rhizotomy, indicating a lack of change in the populations of neurons containing neurotensin-binding sites. This would support the view that up to 50% of GABAB binding sites are located on nerve terminals. The greater reduction in lamina IV after rhizotomy would suggest that GABAB sites may be present on large-diameter afferent fibres that terminate in this region as well as on smaller-diameter C and A delta fibres.

show abstract

“…Although any of the above mechanisms could mediate the enhanced nociception observed in generalized acidosis, the results of the present study suggest an additional mechanism. The soma of DRG neurons expresses GABA-gated channels which elicit responses similar to those elited by GABA application to the terminal region [4,5,15]. Assuming that the receptor channels on the soma are similar to those on the terminals that mediate presynaptic inhibition in the spinal cord, protons could enhance the transmission of nociceptive impulses by inhibition of GABA A receptor channels.…”

mentioning

confidence: 96%

Proton inhibition of GABA-activated current in rat primary sensory neurons

Zhai

Peoples

1998

Pfl�gers Archiv European Journal of Physiology

View full text Add to dashboard Cite

The modulation of the Cl- current activated by gamma-aminobutyric acid (GABA) by changes in extracellular pH in freshly isolated rat dorsal root ganglia (DRG) neurons was studied using the whole-cell patch-clamp technique. In the pH range of 5.0-9.0, increased extracellular pH enhanced, and decreased extracellular pH suppressed, current activated by 10 microM GABA in a reversible and concentration-dependent manner with an IC50 of pH 7.1 in these neurons. Acidification to pH 6.5 inhibited currents activated by the GABAA-selective agonist muscimol in all neurons tested. The antagonism of GABA-activated current by lowering the pH was equivalent at holding potentials between -80 and +40 mV and did not involve a significant alteration in reversal potential. Acidification shifted the GABA concentration/response curve to the right, significantly increasing the EC50 for GABA without appreciably changing the slope or maximal value of the curve. Inhibition of the GABA-activated current by protons was not significantly different when the patch-pipette solution was buffered at pH 7.4 or pH 6.5. These results suggest that extracellular protons inhibit GABAA receptor channels in primary sensory neurons by decreasing the apparent affinity of the receptor for GABA. This represents a novel mechanism of inhibition by protons of a neurotransmitter-gated ion channel. Proton inhibition of GABAA receptor channels may account in part for the modulation by protons of sensory information transmission under certain pathophysiological conditions.

show abstract

Pre- and Non-Synaptic Activities of GABA and Related Amino Acids in the Mammalian Nervous System

Cited by 19 publications

References 146 publications

Characteristics of GABA_B receptor binding sites on rat whole brain synaptic membranes

Characteristics of GABA_B receptor binding sites on rat whole brain synaptic membranes

The location of GABA_B receptor binding sites in mammalian spinal cord

Proton inhibition of GABA-activated current in rat primary sensory neurons

Contact Info

Product

Resources

About

Pre- and Non-Synaptic Activities of GABA and Related Amino Acids in the Mammalian Nervous System

Cited by 19 publications

References 146 publications

Characteristics of GABAB receptor binding sites on rat whole brain synaptic membranes

Characteristics of GABAB receptor binding sites on rat whole brain synaptic membranes

The location of GABAB receptor binding sites in mammalian spinal cord

Proton inhibition of GABA-activated current in rat primary sensory neurons

Contact Info

Product

Resources

About

Characteristics of GABA_B receptor binding sites on rat whole brain synaptic membranes

Characteristics of GABA_B receptor binding sites on rat whole brain synaptic membranes

The location of GABA_B receptor binding sites in mammalian spinal cord