The specificity of strychnine as a glycine antagonist in the mammalian spinal cord

Curtis, D. R.; Duggan, A.W.; Johnston, G. A. R.

doi:10.1007/bf00234248

Cited by 331 publications

(95 citation statements)

References 58 publications

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“…Comparable studies of the influence of bicuculline on GABA log-current response curves can, therefore, prove a useful method of showing cuneate and spinal interneurones to be equally sensitive to the action of bicuculline even though this type of analysis cannot define the drug-receptor interaction (Curtis et at., 1971c). These experiments also showed that the selectivity of bicuculline as a reversible blocker in the cuneate also encompasses a number of structurally related GABA-like amino acids (Curtis et al,197 la).…”

Section: Discussionmentioning

confidence: 99%

On the pharmacology of the γ‐aminobutyric acid receptors on the cuneo‐thalamic relay cells of the cat

Kelly

Renaud

1973

British J Pharmacology

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Summary1. y-Aminobutyric acid (GABA) and glycine applied by iontophoresis were equipotent depressants of cuneo-thalamic relay neurones isolated from the middle third of the cuneate nucleus of cats either decerebrated or anaesthetized with sodium pentobarbitone. 2. Glycine 13+2 nA and GABA 20+2 nA were equipotent depressors of hair cells (n=22) and, bicuculline applied by iontophoresis caused a parallel shift to the right of the GABA but not the glycine log-current response curves. The GABA equipotent dose-ratio was 20 + 0-2 for bicuculline currents of approximately 144 nA lasting about 11 min in cells excited either transynaptically by peripheral stimulation or postsynaptically by glutamate. 3. Although a maximal bicuculline current seldom caused a significant shift of the glycine-log current response curve, many of our records show the onset of the glycine response to be slowed by doses in excess of 84 nA.4. Bicuculline also antagonized depressions by fl-guanidinopropionic acid, and 8-aminovaleric acid which mimicked the action of GABA. 5. When tested on the same neurone, bicuculline and picrotoxin applied by iontophoresis were equipotent and their effects appear to be additive. 6. The GABA sensitivity was not modified by repetitive (5 or 6) doses of i.v. bicuculline (0-2 mg/kg). 7. The antagonism of GABA by bicuculline and picrotoxin appears to be of sufficient specificity to enable the separate roles of GABA and glycine as putative inhibitory transmitters of cuneo-thalamic relav cells to be determined.

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Section: Discussionmentioning

confidence: 99%

On the pharmacology of the γ‐aminobutyric acid receptors on the cuneo‐thalamic relay cells of the cat

Kelly

Renaud

1973

British J Pharmacology

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“…There are considerable problems in the interpretation of dose-response curves obtained from experiments in which drugs are applied by electrophoresis, see Curtis, Duggan & Johnston (1971) and Dionne, Steinbach & Stevens (1978). It was nevertheless felt that this approach might be of value in the comparative study we were attempting to perform.…”

Section: Treatment Of Datamentioning

confidence: 99%

Actions and Interactions of Gaba and Benzodiazepines in the Mouse Hippocampal Slice

Biscoe¹,

Duchen²

1985

Exp Physiol

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SUMMARYIntracellular recordings have been made from CAl, CA3 and dentate cells of the mouse hippocampal slice. y-aminobutyric acid (GABA) and the water-soluble benzodiazepines, midazolam and flurazepam were applied close to the impaled cell somata by microelectrophoresis. GABA always caused a fall in input resistance, although the associated changes in membrane potential were variable. These were consistent with reports which have defined a hyperpolarizing response to somatic and a depolarizing response to dendritic application of GABA to CAl and CA3 cells in the rat and guinea-pig. In this study, the phenomenon was seen in CAl, CA3 and dentate cells. The reversal potential for the hyperpolarizing, somatic response to GABA lay between -70 and -75 mV, similar to the reversal potential ofthe evoked recurrent inhibitory post-synaptic potential (i.p.s.p.). The change in cell input conductance caused by GABA was larger at membrane potentials positive to the resting potential and smaller at hyperpolarized membrane potentials. Extracellular recordings of action potential frequency were made from ten cells in which the application of either midazolam or flurazepam increased the inhibitory potency of GABA. In three of these cells, the benzodiazepine reduced action potential frequency slightly when applied alone. Neither midazolam nor flurazepam had a consistent effect on membrane potential, resting input resistance or the current-voltage (I-V) relations of the cells when ejected alone. In twenty-eight of forty-one cells examined in detail, ejection of either midazolam or flurazepam was found to increase the response to GABA. In six cells, the response to GABA was significantly reduced by the benzodiazepine tested whilst in the remainder, no interaction of the drugs could be demonstrated. Examination of the doseresponse relation for GABA alone and in the presence of midazolam or flurazepam showed that the maximal response to GABA was increased by the benzodiazepine in some cells while it was unchanged in others. When intracellular electrodes were filled with potassium chloride, spontaneous depolarizing GABA-mediated post-synaptic potentials (p.s.p.s) were seen. Measurement of the interval and amplitude distributions of these events showed that flurazepam increased their amplitude but not their frequency.

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“…Also, dopamine is usually found to have an inhibitory action on neurones when applied iontophoretically or topically (McLennan, 1961;Hornykiewicz, 1966;Curtis, Duggan & Johnston, 1971;York, 1972), so the facilitation of the stretch reflex would involve the process of disinhibition or disfacilitation of an inhibitory pathway.…”

Section: Action Of Dopaminementioning

confidence: 99%

A Pharmacological Study of the Adrenergic Mechanisms Involved in the Stretch Reflex of the Decerebrate Rat

Commissiong

Sedgwick

1974

British J Pharmacology

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1The effects of catecholamine precursors, enzyme inhibitors, and monoamine depletors have been studied on the stretch reflex in the decerebrate rat. 2 L-DOPA alone had a biphasic effect, facilitation followed by inhibition and recovery of the reflex.3 About 10% of the preparations did not develop decerebrate rigidity. These preparations did not have a stretch reflex. Within 1 to 5 min of the injection of L-DOPA in these inactive preparations, a stretch reflex could be elicited. 4 Control experiments indicate that L-DOPA was acting centrally after decarboxylation. 5 D L-dihydroxyphenylserine had an inhibitory effect, without a preceding facilitation. 6 When L-DOPA was preceded by diethyldithiocarbamate (i.v.) or FLA-63 (i.p.), the predominant response was a sustained facilitation, without an accompanying inhibition. 7 It is concluded that in the decerebrate rat, increased stretch reflex activity is associated with increased central levels of dopamine, and decreased stretch reflex activity with increased central levels of noradrenaline. The results are discussed with reference to the possibility that dopamine acts by liberating 5-hydroxytryptamine.

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The specificity of strychnine as a glycine antagonist in the mammalian spinal cord

Cited by 331 publications

References 58 publications

On the pharmacology of the γ‐aminobutyric acid receptors on the cuneo‐thalamic relay cells of the cat

On the pharmacology of the γ‐aminobutyric acid receptors on the cuneo‐thalamic relay cells of the cat

Actions and Interactions of Gaba and Benzodiazepines in the Mouse Hippocampal Slice

A Pharmacological Study of the Adrenergic Mechanisms Involved in the Stretch Reflex of the Decerebrate Rat

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