Ventral Root Responses of the Hemisected Amphibian Spinal Cord to Perfused Amino Acids in the Presence of Procaine

Evans, Richard H.; Watkins, Johnathan

doi:10.1111/j.1476-5381.1975.tb07427.x

Cited by 52 publications

(13 citation statements)

References 20 publications

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“…Similar conclusions were reached in studies on amphibian spinal cord in vitro (Barker et al, 1975, Evans & Watkins, 1975Nicoll et al, 1976), except that strychnine does not antagonize glycine-induced depolarization of primary afferent terminals (Barker et al, 1975) or motoneurones (Evans, Francis & Watkins, 1976). Table 1 gives dose-ratios for antagonism obtained at different concentrations of the antagonists when applied to 14 hemisected immature rat spinal cord preparations.…”

Section: Neutral Amino Acidssupporting

confidence: 57%

“…Preparations were stable for 12 h but, unlike the frog spinal cord (Evans & Watkins, 1975), they did not survive for periods longer than 24 hours. L-Gluta- mate and related amino acids caused depolarizing DR and VR responses, the mean potency of the compounds on the VR response relative to L-glutamate being as follows (number of preparations in parentheses): quisqualate 410(4), kainate 380(3), N-methyl-D-aspartate 100(3), L-homocysteate 23(13), L-glutamate 1, L-aspartate 1(6).…”

Section: Resultsmentioning

confidence: 99%

“…Glycine and GABA cause membrane hyperpolarization of mammalian motoneurones in vivo (Curtis, Hosli, Johnston & Johnston, 1968) and GABA, taurine and P-alanine hyperpolarize frog motoneurones in vitro (Evans & Watkins, 1975;Nicoll, Padjen & Barker, 1976). All four amino acids depolarize primary afferent terminals of amphibian spinal cords (Barker, Nicoll & Padjen, 1975), while GABA similarly depolarizes primary afferent terminals of the isolated immature rat spinal cord (Otsuka & Konishi, 1976a) and both GABA and glycine also depolarize motoneurones in this preparation (Otsuka & Konishi, 1976b).…”

Section: Neutral Amino Acidsmentioning

confidence: 99%

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The Effects of Amino Acids and Antagonists on the Isolated Hemisected Spinal Cord of the Immature Rat

Evans¹

1978

British J Pharmacology

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1 Records of ventral and dorsal root polarity of the isolated hemisected spinal cord of the 3-9 day old rat showed that respective dose-dependent depolarizations of motoneurones (VR responses) and primary afferent terminals (DR responses) were produced by both acidic and neutral amino acids in the presence of procaine (1 mM) or tetrodotoxin (0.1 gM).2 Of the four neutral amino acids, y-aminobutyrate (GABA), glycine, taurine, and ,B-alanine, GABA was the most effective in producing DR responses and glycine the most effective in producing VR responses. Only taurine depressed the electrical activity recorded from ventral roots. 3 The DR responses produced by GABA, ,B-alanine and taurine. were all antagonized by bicuculline (5 gM) and picrotoxin (5 gM). Bicuculline was more selective than picrotoxin in antagonizing VR responses produced by GABA.4 Strychnine (1 gM) antagonized VR responses produced by glycine P-alanine and taurine without affecting responses produced by GABA. DR responses to the neutral amino acids were unaffected by strychnine.

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Section: Neutral Amino Acidssupporting

confidence: 57%

Section: Resultsmentioning

confidence: 99%

Section: Neutral Amino Acidsmentioning

confidence: 99%

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The Effects of Amino Acids and Antagonists on the Isolated Hemisected Spinal Cord of the Immature Rat

Evans¹

1978

British J Pharmacology

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“…Carbamylcholine, which induces rhythmical bursting activity more clearly than does acetylcholine (7), was employed as a cholinergic agonist to elucidate the cholinergic mechanisms involved in the spinal motor function. In Call-free, Mg2+ (9 mM)-Ringer's solution, however, the depolarizing effect of acetylcholine could not be observed as has been shown in the procaine pretreated preparation (9). Serotonin had no depolarizing action on motoneurons as was also reported by Shirasawa and Koketsu (10).…”

Section: Effects Of Cholinomimeticssupporting

confidence: 60%

Effects of Excitatory Transmitter Candidates on Frog Spinal Motor Function

Kim

Kudo

Fukuda

1979

Japanese Journal of Pharmacology

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Abstract-Thepropriospinal motor function of the frog spinal cord was investigated pharmacologically in the isolated spinal cord-nerve-muscle preparation.In the preparation with a pair of antagonistic muscles, the tissues showed reciprocal con tractions in response to the spontaneous discharges from the ventral root. M. tibialis anterior responded to the discharges from the ventral root and showed slow con tractions.Contractions of the m. gastrocnemius were much less frequent but the movement was rapid and strong. The addition of acetylcholine (10-4-10-3 M) to the medium, perfusing the spinal cord, resulted in a predominant excitation of m. tibialis anterior.Carbamylcholine (10-s M) and bethanechol (10-4 M) induced rhythmical contractions in m. tibialis anterior and depressed the movement of m. gastrocnemius. These effects were blocked by atropine (10-5 M). Serotonin (10-5 M) exerted a strong facilitatory effect on both muscles which contracted reciprocally during this treatment. L-Glutamate (10-4-10-3 M) induced a transient synchronous contraction in both muscles. By means of the sucrose-gap method, cholinomimetics and serotonin proved to have no direct effect on the motoneuron, while L-glutamate had a direct effect. Results suggest that propriospinal controlling mechanisms, regulated via serotonergic and cholinergic pathways exist and drive co-ordinate muscle movement.Investigations on functional organization of the spinal motor system have been done from physiological and anatomical points of view (1-4). It was demonstrated in the am phibian that the spinal cord has the ability to produce the general pattern of stepping without receiving the controls from the higher center and signals from the peripheral sensory organs (3). There is, however, little pharmacological documentation. We attempted to ascertain physiological and anatomical aspects on the propriospinal motor control system from a pharmacological point of view.In the present study, we employed the isolated spinal cord preparation (5, 6) and the preparation with innervated muscles (7). As the preparation with two antagonistic muscles was found to maintain reciprocal contractions following spontaneous discharges from the spinal cord, the preparation was thought to be appropriate for investigating the motor function. The effects of excitatory transmitter candidates on the preparation were examined and the possible roles of these candidates on the motor control system of the amphibian spinal cord are discussed.

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“…However, interpretation of the amphibian results was complicated by the fact that the ventral root responses were compounded of both direct actions of the added substances on the motoneurones and indirect effects on neurones forming part of synaptic pathways terminating on motoneurones. This difficulty has recently been overcome by the inclusion in the perfusion medium of procaine, tetrodotoxin or a high Mg2+ concentration, all of which prevent synaptically relayed effects, so restricting the responses of the ventral roots to the direct actions of the amino acids on motoneurones (Barker & Nicoll, 1973;Konishi & Otsuka, 1974;Barker, Nicoll & Padjen, 1975;Evans & Watkins, 1975a). Using the procaine-containing system we have tested an extensive series of excitants covering a wide range of related structures and established an order of potency for the compounds on frog motoneurones.…”

Section: Present Address: John Curtin School Of Medical Researchmentioning

confidence: 99%

Structure‐activity Relations of Excitatory Amino Acids on Frog and Rat Spinal Neurones

Biscoe

Evans

Headley

et al. 1976

British J Pharmacology

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195

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I A series of compounds structurally related to glutamic acid has been tested on frog and rat spinal neurones. The substances were added to procaine-containing medium bathing the isolated hemisected spinal cord of the frog, and their potencies in depolarizing motoneurones were assessed by the magnitude of the potential produced in the ventral root. The electrophoretic technique was used to administer the substances around single interneurones of the rat spinal cord and the relative potencies of the compounds as excitants assessed by the magnitude of the currents required to produce similar rates of neuronal firing. 2 Parallel structure-activity relations were observed in the two series of experiments, suggesting that the receptors for excitatory amino acids on frog and rat spinal neurones are similar. 3 Quisqualate, domoate and kainate were the strongest excitants in both animals, with potencies around two orders of magnitude higher than that of L-glutamate. 4 2,4,5-Trihydroxyphenylalanine (6-OH-DOPA) was a stronger excitant and L-3,4-dihydroxyphenylalanine (L-DOPA) a weaker excitant than L-glutamate on frog spinal motoneurones. The former compound was also a more potent convulsant than L-glutamate on intraventricular injection into mouse brain. The lack of activity of 6-OH-DOPA on electrophoretic administration was attributed to oxidation. SUnlike the majority of amino acid excitants, several of the compounds shown in the present work to have moderate excitatory activity are not anionic at physiological pH. This indicates either that two negatively charged groups are not essential for interaction with a common excitatory receptor, or that more than one type of receptor is involved in the actions demonstrated.

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Ventral Root Responses of the Hemisected Amphibian Spinal Cord to Perfused Amino Acids in the Presence of Procaine

Cited by 52 publications

References 20 publications

The Effects of Amino Acids and Antagonists on the Isolated Hemisected Spinal Cord of the Immature Rat

The Effects of Amino Acids and Antagonists on the Isolated Hemisected Spinal Cord of the Immature Rat

Effects of Excitatory Transmitter Candidates on Frog Spinal Motor Function

Structure‐activity Relations of Excitatory Amino Acids on Frog and Rat Spinal Neurones

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