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

Abstract

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.

PRESYNAPTIC ACTIONS OF Β‐AMINOBUTYRIC ACID AND SOME ANTAGONISTS IN a SLICE PREPARATION OF CUNEATE NUCLEUS

“…The concentrations required were high, as also found for leptazol on frog spinal cord (Nicoll & Padjen, 1976), so it is not surprising that no effect was obtained 10mM 1mM U I n, 0.4r with microiontophoretic applications in vivo (Hill et al, 1976), although iontophoretic leptazol has been reported to antagonize GABA on cultured mouse spinal cord neurones (Macdonald & Barker, 1977).…”

Depolarizing responses to glycine, β‐alanine and muscimol in isolated optic nerve and cuneate nucleus

“…The close similarity in properties between the glycine receptors on optic nerve and those studied in vivo (Curtis et al, 1971;Hill et al, 1976) suggests that the rat optic nerve preparation will be a useful in vitro system for quantitative studies of the mammalian neuronal glycine receptor plus ionophore complex.…”

“…The main distinguishing feature is that responses to glycine are much more readily blocked by strychnine than are responses to GABA (Curtis, Duggan, Felix, Johnston & McLennan, 1971;Hill, Simmonds & Straughan, 1976). The potencies and sites of action of several GABA antagonists have been determined on isolated preparations of rat cuneate nucleus (Simmonds, 1982) but comparable quantitative information for glycine was not obtained from this preparation due to the small size of the glycine responses.…”

Patch‐clamp analysis of glycine‐induced currents in chick ciliary ganglion neurons.

“…Bicuculline is a competitive antagonist of GABAA receptors, but its specificity has been questioned (Hill, Simmonds & Straughan, 1976;Zhang & Feltz, 1991 (Nicoll, 1975;Hill et al 1976;Lebeda, Hablitz & Johnston, 1982;Bixby & Spitzer, 1984). dTC inhibited responses induced by 40 /M glycine from ciliary ganglion neurons in a dose-dependent manner (Fig.…”