Properties of γ-aminobutyric acid (GABA) receptor binding in rat brain synaptic membrane fractions

Enna, S.J.; Snyder, Solomon H.

doi:10.1016/0006-8993(75)90243-7

Cited by 631 publications

(193 citation statements)

References 29 publications

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“…Changes in external K can produce shifts in the equilibrium potentials for the responses to glycine and GABA in frog motoneurones, but these shifts are probably due to changes in internal Cl concentrations in accord with the new resting potentials (Velumyan et al 1977). The conductance increases produced by synaptic inhibition in the spinal cord are at least dominated by Cl, since reflex inhibition in the isolated rat cord disappears in Cl-free fluid (Otsuka & Konishi, 1974), and since seizures are produced in Cl-free fluid in the frog spinal cord (Kudo, Abe, Goto & Fukuda, 1975) (Young & Snyder, 1973 and binding of [3H]GABA (Zukin, Young & Snyder, 1974;Enna & Snyder, 1975) (Enna, Collins & Snyder, 1977) or from the frog (Enna & Snyder, 1977). Thus, the antagonistic effects of drugs and amino acids observed in the present electrophysiological experiments agree with the results of chemical binding.…”

Section: Discussionmentioning

confidence: 99%

“…[3H]GABA reaches half saturation in Na-free medium at 0O03-0 4 fZM (Enna & Snyder, 1975, while initial inhibition of interneuronal discharges in the lamprey spinal cord occurs at 10 #M. These differences might be explained in part by (a) a lower concentration of the amino acids around nerve cells in the present experiments due to transport by the spinal cord and (b) a decreased effect of low concentrations of glycine and GABA due to co-operativity, in which the conductance change increases as a power function of receptor binding (Werman, 1969). The affinity of isolated membranes of the rat central nervous system for [3H]strychnine is very high, 2*7-30 nm for half-maximal binding (Young & Snyder, 1973.…”

Section: Discussionmentioning

confidence: 99%

“…A simple and attractive model is a receptor which requires the binding of two or more transmitter molecules in order to activate the unitary conductance. Binding of the molecules themselves can be independent, as with [3H]GABA to membrane fractions (degree of co-operativity 0*9; Enna & Snyder, 1975), or some interaction may occur, as with displacement of bound strychnine by glycine (degree of glycine co-operativity 1-7;. However, any metabolic processes or experimental artifacts which reduce the effects of drugs at low concentrations or enhance them at high concentrations will introduce or exaggerate an apparent co-operativity.…”

Section: Discussionmentioning

confidence: 99%

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Conductance increases produced by glycine and gamma‐aminobutyric acid in lamprey interneurones.

Homma¹,

Rovainen²

1978

The Journal of Physiology

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SUMMARY1. Conductances of individual neurones in the isolated lamprey spinal cord were measured with separate intracellular electrodes for recording potentials and for passing current pulses during application of glycine or GABA (0.1-1.0 mM) in Cafree bathing fluid. Large, reversible increases in conductance were produced in giant interneurones by both amino acids, but Muller axons and sensory dorsal cells were unaffected.2. Conductance increases produced by glycine and by GABA were selective for C1. Both conductance increases were linearly related to external Cl concentrations and repeated exposure to the amino acids in Cl-free fluid progressively reduced the conductance increases to less than 1 % of their values in normal C1.3. Strychnine was a competitive antagonist of glycine, while GABA was antagonized competitively by bicuculline and non-competitively by picrotoxin.4. The sensitivity of giant interneurones to glycine and GABA increased at low temperatures, in Na-free fluid, and after repeated exposure to the amino acids. Sensitization may have been produced by inhibition of uptake mechanisms for glycine and GABA in the spinal cord.5. Discharges of interneurones recorded extracellularly were inhibited by bathapplied glycine and GABA, but directly elicited action potentials of axons were ,unaffected. Strychnine and Cl-free fluid in the presence of Ca produced seizures in lamprey spinal cord.6. The conclusions of these experiments are that different receptors for glycine and for GABA are present on giant interneurones, that glycine is the better candidate for an inhibitory transmitter in the lamprey spinal cord, and that GABA produces effects similar to those which have been well studied in arthropod muscle.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Conductance increases produced by glycine and gamma‐aminobutyric acid in lamprey interneurones.

Homma¹,

Rovainen²

1978

The Journal of Physiology

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“…The possibility that ibotenate might interact with central GABA receptors was studied by examining its influence on the sodium independent binding of [3H]GABA (4.6 x 10-9M) by rat brain membranes (Enna & Snyder, 1975 The excitation of Renshaw cells by acetylcholine was also reduced following ibotenate. With all three neurones tested both the response to electrophoretic acetylcholine and that to ventral root stimulation were reduced more or less in parallel with those to an excitant amino acid.…”

Section: Methodsmentioning

confidence: 99%

The excitation and depression of spinal neurones by ibotenic acid.

Curtis¹,

Lodge²,

McLennan³

1979

The Journal of Physiology

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SUMMARY1. The firing of spinal interneurones and Renshaw cells by microelectrophoretic (± )-ibotenate, which was approximately eight times more active as an excitant than L-glutamate, was followed by prolonged depression of the sensitivity of the neurones to excitant amino acids and acetylcholine.2. The depression, which lasted for 15-30 min when ibotenate was ejected for 3-6 min, was blocked by the GABA-antagonist bicuculline methochloride, and was independent of prior firing since it occurred with subthreshold concentrations of ibotenate and when ibotenate firing had been blocked by DL-a-aminoadipate. 3. When administered electrophoretically for 5 min, muscimol, a potent GABA agonist, reduced neuronal excitability for prolonged periods and this effect was also prevented by bicuculline methochloride.4. The depression of neuronal excitability produced by GABA, taurine, isoguvacine or 3-aminopropane sulphonate, ejected for periods of 5-6 min, recovered rapidly.5. It is suggested that ibotenate is converted in vivo to muscimol or a related compound which has a prolonged, bicuculline-sensitive depressant action on the excitability of neurones.

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“…GABA is the major inhibitory neurotransmitter of the mammalian brain; it mediates its effects via specific interaction with integral membrane proteins, the GABA receptors. [13][14][15][16] Several case/control association studies have suggested that the GABA A subunit gene cluster on 5q33, namely the GABA A b2, GABA A a6, GABA A a1 and GABA A g2 subunit genes, may play a role in the development of alcoholism in different ethnic populations. [17][18][19][20] The association of these genes and alcoholism appears to be different between populations and clinical phenotypes.…”

Section: Introductionmentioning

confidence: 99%

Gender-specific contribution of the GABAA subunit genes on 5q33 in methamphetamine use disorder

et al. 2003

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Family and twins studies have suggested that genetic factors are involved in the development of substance use disorders. Several unrelated case/control association studies have reported associations of the GABA A subunit genes on 5q33 with the development of alcohol dependence. We hypothesized that these particular GABA A subunit genes also contribute to the development of methamphetamine use disorder. To test our hypothesis, we recruited cases using a series of questionnaires. Among the polymorphic SNPs, significant differences between cases and controls were identified in the female sample in the rs2279020 of the GABA A a1 subunit gene, and the novel SNP rs4480617 in the GABA A g2 subunit gene. No associations were found in the male sample. Further haplotype analysis identified several marker blocks significantly associated with methamphetamine use disorder in females; each block consists of the rs4480617. Our study provides preliminary evidence that the GABA A subunit genes on 5q33 may preferentially contribute to methamphetamine use disorder in females. There is increasing evidence that substance use disorders are familial and that genetic factors explain a substantial degree of the familial aggregation. 3 Grove et al 4 studied a sample of 32 pairs of monozygotic twins reared apart, and reported that inherited factors explained 45% of the variance in drug abuse and dependence. Pickens et al 5 found that the variance attributable to genetic factors in abuse of illicit drugs is 31% in males and 22% in females. Similarly, Tsuang et al 6 reported that genetic factors account for 34% of the variance in the individual's risk of developing a drug use disorder; for stimulant abuse, 44% of the variance is attributable to genetic factors. The pairwise concordance rate for stimulant abuse was 14.1% for monozygotic twins and 5.3% for dizygotic twins. 7 The supporting evidence is also derived from animal studies. For example, knockout of the dopamine D4 receptor gene in mice result in animals that are supersensitive to several substances, including methamphetamine. 8 For the GABA A a1 knockout mice, administration of amphetamine sulfate caused an

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Properties of γ-aminobutyric acid (GABA) receptor binding in rat brain synaptic membrane fractions

Cited by 631 publications

References 29 publications

Conductance increases produced by glycine and gamma‐aminobutyric acid in lamprey interneurones.

Conductance increases produced by glycine and gamma‐aminobutyric acid in lamprey interneurones.

The excitation and depression of spinal neurones by ibotenic acid.

Gender-specific contribution of the GABAA subunit genes on 5q33 in methamphetamine use disorder

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