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

Kelly, John; Renaud, Leo P.

doi:10.1111/j.1476-5381.1973.tb08346.x

Cited by 49 publications

(15 citation statements)

References 48 publications

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“…Their experimental design and method of quantitative analysis were different from our own and may have allowed the reported selectivity towards GABA to become more apparent. For example, Kelly & Renaud (1973a) observed that 'Although in general, bicuculline seldom caused a significant shift of the glycine log-current response curve, many of our records showed bicuculline to slow the onset of the response to glycine'. This was interpreted by the authors to mean that (+)-bicuculline did not antagonize glycine.…”

Section: Experimentalproceduresmentioning

confidence: 99%

Antagonism of Γ‐aminobutyric Acid and Glycine by Convulsants in the Cuneate Nucleus of Cat

Hill

Simmonds

Straughan

1976

British J Pharmacology

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1Some convulsant substances have been applied-to single neurones in the cat cuneate nucleus by microiontophoresis. Numerical values were derived for the effectiveness and selectivity of the substances as antagonists of y-aminobutyric acid (GABA) and glycine. 2 (+)-Bicuculline methochloride was the most effective GABA antagonist and it also excited many neurones. It antagonized GABA in 93% of experiments but also antagonized glycine in 41% of experiments. In most experiments the antagonism of GABA was greater than the antagonism of glycine resulting in an overall selective antagonism of GABA that was statistically significant. Nevertheless, in only about one quarter of the individual experiments was the GABA antagonism substantial and the selectivity clearcut. 3 (+)-Bicuculline and picrotoxin were less easily applied to neurones by microiontophoresis and were found to antagonize GABA in 30% and 35% of experiments, respectively. They also antagonized glycine in 25% and 30% of experiments, respectively. Overall, neither substance could be shown to be selective, statistically, although in the few individual experiments where the GABA antagonism was substantial the antagonism was clearly selective. 4 (+)Tubocurarine antagonized GABA in 59% and glycine in 32% of experiments and it also excited many neurones. Penicillin antagonized GABA in 33% of experiments without antagonizing glycine. Neither antagonist caused any substantial antagonisms of GABA and neither showed significant selectivity overall. (-)-Bicuculline methochloride, leptazol and bemegride antagonized GABA or glycine in less than 10% of experiments, although (-)-bicuculline methochloride excited most neurones. SStrychnine antagonized glycine in every experiment while antagonizing GABA in only 5% of experiments. In each individual experiment the antagonism of glycine was substantial and clearly selective, resulting in a statistically significant selectivity overall. 6 It is concluded that the selective glycine antagonist strychnine is considerably better than the presently available GABA antagonists for distinguishing between responses to GABA and glycine, when the antagonists are applied by microiontophoresis.

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Section: Experimentalproceduresmentioning

confidence: 99%

Antagonism of Γ‐aminobutyric Acid and Glycine by Convulsants in the Cuneate Nucleus of Cat

Hill

Simmonds

Straughan

1976

British J Pharmacology

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“…Before strychnine, log-current response curves showed 50% depression to be produced by glycine 13 nA and ,8-alanine 23 nA. The slope of the P-alanine curve was only one third as steep as that for glycine and therefore resembles that of GABA curves described in the preceding paper (Kelly & Renaud, 1973a). Three minutes after the onset of the 6 min strychnine application the slope of the glycine and 8-alanine log-current response curves was unaltered, however, they were equally displaced to the right by a distance equivalent to an equipotent dose-ratio of 2.…”

Section: Resultsmentioning

confidence: 75%

“…In the preceding paper (Kelly & Renaud, 1973a), the response to glycine was shown to be almost unaffected by applications of bicuculline and picrotoxin which caused a nearly two-fold reduction in the GABA sensitivity of the postsynaptic cell. The glycine sensitivity of cuneate neurones can, however, be blocked very effectively by relatively brief applications of strychnine with currents 4 or 5 times smaller than those used to release GABA antagonists.…”

Section: Resultsmentioning

confidence: 99%

“…The construction of log-current response curves and the calculation of the equipotent ratio is described in the preceding paper (Kelly & Renaud, 1973a).…”

Section: Log-current Response Curvesmentioning

confidence: 99%

“…In the preceding paper (Kelly & Renaud, 1973a) y-aminobutyric acid (GABA) and glycine were shown to be almost equally effective depressants of the activity of cuneate neurones excited either postsynaptically by glutamate or transynaptically by peripheral stimulation. The action of GABA but not glycine, was effectively blocked by iontophoretic release of bicuculline and picrotoxin.…”

Section: Introductionmentioning

confidence: 99%

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On the pharmacology of the glycine receptors on the cuneo‐thalamic relay cells in the cat

Kelly

Renaud

1973

British J Pharmacology

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Summary1. In cats either decerebrated or anaesthetized with sodium pentobarbitone, strychnine released by iontophoresis from electrodes containing a 5 mm solution in 165 mm of NaCl, abolished the action of glycine and f3-alanine on cuneo-thalamic relay cells without disturbing their response to equally effective applications of y-aminobutyric acid (GABA) and i3-guanidino-propionic acid.2. The loss of glycine sensitivity appeared to increase as long as the strychnine release continued until even the largest currents tolerated by the electrode were unable to eject effective amounts of glycine. Parallel shifts of the glycine log-current response curves, equivalent to an equipotent dose-ratio of about 2-0 only occurred when the duration of the strychnine applications by current in excess of 28 nA was restricted to a few minutes. 3. Without modifying either the frequency of the spike discharge or the amplitude or shape of the action potential, currents larger than 28 nA occasionally caused a loss of GABA sensitivity. 4. Strychnine administered either intravenously (02 mg/kg) or applied topically to the surface of the cuneate (05 mM) blocked the response to glycine without any obvious effect on the response to GABA. 5. It was concluded that the discovery of a strychnine-sensitive component of the inhibitory potentials recorded from the cuneate nucleus will reveal the physiological role of the glycine receptors on cuneo-thalamic relay cells.

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Biochemistry and Physiology of Amino Acid Transmitters

Obata

1977

Comprehensive Physiology

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

Cited by 49 publications

References 48 publications

Antagonism of Γ‐aminobutyric Acid and Glycine by Convulsants in the Cuneate Nucleus of Cat

Antagonism of Γ‐aminobutyric Acid and Glycine by Convulsants in the Cuneate Nucleus of Cat

On the pharmacology of the glycine receptors on the cuneo‐thalamic relay cells in the cat

Biochemistry and Physiology of Amino Acid Transmitters

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