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T A James

Publications and source records attributed to T A James.

16 recordsLinked to original sources

Is glycine an inhibitory synaptic transmitter in the substantia nigra?

Nigral tissue accumulated 14C-glycine by an energy-, temperature- and sodium-dependent mechanism; the transport process was inhibited by small neutral amino acids and had an apparent Km of 143 microM and Vmax of 787 nmol/g/min. Re-release of accumulated 14C-glycine was initially extremely rapid (40% in first 5 min) and subsequently accelerated by +40 mM K+ in a Ca2+-dependent manner. Intranigral kainate (0.25 microgram) lowered the levels of striatal DA (63%) and nigral GABA (25%) ipsilaterally, but not nigral glycine. Injections of glycine or strychnine (10--100 micrograms) into one SN induced slow ipsiversive or contraversive turning respectively. The evidence for glycine as a neurotransmitter in SN is discussed.

Amino Acids

Rapid behavioural and biochemical effects of tetanus toxin microinjected into the substantia nigra: a dual role for GABA?

Tetanus toxin (200--250 mouse lethal doses) microinjected unilaterally into the substantia nigra produced rapid behavioural and biochemical effects. If the toxin was injected into the rostral part of the substantia nigra (SN), contralateral turning was observed. Raised ipsilateral striatal levels of the dopamine (DA) metabolite, homovanillic acid (HVA), indicated that this turning was due to activation of the nigro-striatal dopamine system. Caudal nigral injections of tetanus toxin produced ipsilateral turning. Biochemical estimations suggest that this behaviour change was mediated by a non-dopamine (non-DA) pathway.

Animals

Effects of substance P injected into the substantia nigra.

1 Behavioural and biochemical effects of substance P (SP, 1 to 10 mug) administered in a small volume to discrete areas of the rat's brain were studied by means of a refined microinjection technique.2 SP injected unilaterally into the zona reticulata of the substantia nigra elicited dose-dependent contraversive circling and an increase in dopamine turnover in the ipsilateral striatum. SP applied to the zona compacta or zona lateralis, or to the medial lemniscus, evoked ipsiversive turning with a fall in dopamine turnover and a rise in 5-hydroxytryptamine (5-HT) turnover in the corresponding striatum.3 In both cases the onset of turning was immediate, reached a peak at about 5 min and lasted for 10 min. Both types of behaviour were blocked by haloperidol and exaggerated by nialamide.4 Unilateral injections of SP given into the crus cerebri, zona incerta, caudate nucleus, putamen or globus pallidus did not modify the animal's behaviour.5 In rats pretreated with apomorphine or amphetamine, SP induced contraversive circling which was followed by locomotion in the opposite direction.6 Turning responses to a second dose of SP were diminished at 3 h and reproducible at 24 h after the first injection.7 Bacitracin (50 ng) injected into the zona reticulata caused ipsiversive turning. Larger intranigral doses of bacitracin (10 mug), as with intracisternal SP (10 mug), evoked ;barrel rotation'.8 No changes in the free concentrations of aspartate, glutamate, gamma-aminobutyric acid, glycine or alanine were detected in any brain region following an intracisternal injection of 10 mug SP, although glutamine levels were elevated throughout the brain 30 to 60 min later.

Animals

Potentiation by substance P of contractions of the isolated vas deferens of the mouse elicited by electric field stimulation and by drugs.

1 Isolated vasa deferentia from the mouse were opened longitudinally and suspended in Krebs solution at 37 degrees C in an organ bath. Contractions of the muscle were elicited by electric field stimulation, noradrenaline (10(-6) M) and acetylcholine (10(-6) M). Continued transmural stimulation evoked a biphasic response comprising a rapid twitch followed about 10 s later by a smaller, sustained rise in muscle tone.2 The amplitudes of nerve-mediated and drug-induced responses were considerably potentiated by substance P (SP) in the dose range 10(-12) to 10(-7) M. Higher concentrations of SP were directly spasmogenic. The sensitizing property of SP was dose-dependent and was usually well maintained, but always disappeared quickly on washing the preparation. In some experiments SP facilitated the twitch, but not the subsequent phase of the electrically-induced contraction or the response to externally applied noradrenaline.3 Phentolamine (10(-6) M) failed to block this effect of SP, but itself potentiated the nerve-mediated twitch, and completely abolished the sustained secondary contraction.4 Desmethylimipramine (10(-6) M) enhanced the delayed contraction but not the immediate contraction.5 The uptake of tritiated noradrenaline (3 x 10(-7) M) by vasa was inhibited by desmethylimipramine (10(-6) M) and increased by nialamide (3 x 10(-5) M), but was not modified by SP (10(-6) M).6 Nerve-mediated release of accumulated radioactivity was accelerated by phentolamine, but not by SP or desmethylimipramine.7 These findings suggest that SP sensitizes the muscle cells to depolarizing stimuli but that it has no facilitatory effect on sympathetic neural elements.

Animals

The nature of potassium chloride-induced relaxations of the rat anococcygeus muscle.

1. The nature of KCl-induced relaxations of the rat anococcygeus muscle was investigated. 2. The relaxations were mimicked by other K+ salts, but not by NaCl. 3. The muscle was more susceptible to the relaxant effects of KCl than the contractile effects. 4. Addition of ouabain (100 micron) had no effect on the relaxations. 5. The relaxations were abolished by tetrodotoxin (5 microgram/ml), procaine (500 micron), and by section of the inhibitory nerves. 6. The results suggest that KCl-induced relaxations are due to stimulation of the inhibitory nerves by K+.

Animals