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Biomedical subjects

T W Stone

Publications and source records attributed to T W Stone.

At least 271 records · Page 15Linked to original sources
PubMed1978

Antagonism by clonidine of neuronal depressant responses to adenosine, adenosine-5'-monophosphate and adenosine triphosphate.

1. Adenosine and its nucleotides adenosine-5'-monophosphate (AMP) and adenosine triphosphate (ATP) have been applied by microiontophoresis to neurones in the cerebral cortex of rats anesthetized with urethane. The firing rate of most neurones was depressed, though two cells were encountered which showed biphasic responses to ATP consisting of an initial excitation succeeded by depression. 2. The application of clonidine with iontophoretic currents of less than 25 nA resulted in blockade of the depressant responses to the purines, without affecting responses to noradrenaline, 5-hydroxytryptamine or gamma-aminobutyric acid (GABA). At much higher doses of clonidine, direct depression of cell firing occurred and occasional interaction with noradrenaline was noted. 3. In the case of the biphasic responses to ATP, clonidine seemed to block only the depressant phase. Reduction of the excitatory component paralleled changes of background firing. 4. It is concluded that, in common with some other 2-substituted imidazoline derivatives, clonidine possesses the ability to block responses to purine compounds.

Adenine Nucleotides↗
PubMed1977

Microiontophoretic studies of the effects of cylic nucleotides on excitability of neurones in the rat cerebral cortex.

1. Responses of cerebral cortical neurones to the microiontophoretic application of acetylcholine, noradrenaline, cyclic adenosine 3',5'-monophosphate (cyclic AMP) and cyclic guanosine 3',5'-monophosphate (cyclic GMP) were examined.2. The application of acetylcholine and cyclic GMP to identified pyramidal tract neurones resulted in an increased frequency of firing in a large number of cells. Upon application of both substances to cells which could not be identified as pyramidal tract cells, a reduction in the frequency of spontaneous firing was sometimes observed.3. Careful current controls had no effect on the cells discussed here, indicating that the observed responses were not due to the iontophoretic currents. Also, the electro-osmotic ejection of cyclic GMP (outward current) produced similar changes of cell firing to those which followed iontophoretic application (inward current).4. The microiontophoretic application of atropine resulted in a blockade of acetylcholine responses while leaving responses to cyclic GMP unaffected. This suggests that cyclic GMP was not acting indirectly by releasing acetylcholine from presynaptic endings.5. Ejection of cyclic GMP from solutions containing calcium ions produced responses comparable to those produced by cyclic GMP alone. It is unlikely therefore that cyclic GMP was causing excitation by chelating calcium.6. Applications of noradrenaline and cyclic AMP produced a reduction in the spontaneous discharge rate of most neurones tested.7. Phosphodiesterase inhibitors such as ICI 63,197 caused a potentiation of the noradrenaline responses of pyramidal tract neurones.8. 5'-adenosine monophosphate produced a powerful depression of all cells to which it was applied. This action was blocked by aminophylline, suggesting the effect was mediated through an adenosine receptor. Responses to cyclic AMP were usually not abolished, but were reduced by about 50% in amplitude.9. These results are consistent with the hypothesis that cyclic AMP may mediate some neuronal effects of noradrenaline and cyclic GMP may mediate some effects of acetylcholine. The results are also consistent with the suggestion that the two nucleotides may sometimes mediate opposite cellular responses to humoral stimuli.

Acetylcholine↗
PubMed1977

The nature of adrenoceptors in the guinea pig cerebral cortex: a microiontophoretic study.

1. Noradrenaline, isoprenaline, and phenylephrine have been applied my microiontophoresis to neurones in the guinea pig cerebral cortex. All three compounds produced depression of neuronal firing, and all could be antagonized to some extent by phentolamine or propranolol. 2. The responses to isoprenaline were substantially reduced in size after a few applications. Noradrenaline and phenylephrine responses were partially reduced at the time of isoprenaline insensitivity, and the responses could now be blocked completely by phentolamine. 3. The results suggest that two kinds of receptors are present in the guinea pig cerebral cortex, with properties similar to alpha and beta receptors in the periphery. A single receptor with intermediate properties would not readily explain the present results. 4. The results are not consistent with the proposal that alpha receptors mediate neuronal excitation, and beta receptors inhibition in the cerebral cortex. 5. It is also suggested that the failure of some previous studies on guinea pig cortex in vitro to demonstrate the presence of beta receptors may be due to the particularly rapid desensitization of these receptors.

Animals↗
PubMed1976

Is glutamic acid the pyramidal tract neurotransmitter?

Applied by microiontophoresis, 1-hydroxy-3-amino-pyrrolidone-2 (HA-966) antagonized excitation by glutamic acid but not by acetylcholine of neurones in the rat cuneate nucleus. HA-966 blocked the short latency excitation of cuneate neurones following stimulation of the pyramidal tract on 28 of 40 cells (70%). Thus, glutamate or a related amino-acid may be the neurotransmitter released by pyramidal tract neurones.

Acetylcholine↗
PubMed1976

Responses of neurones in the cerebral cortex and caudate nucleus to amantadine, amphetamine and dopamine.

1. Dopamine amantadine and amphetamine have been applied directly by microiontophoresis to single neurones in the caudate nucleus and cerebral cortex of rats anaesthetized with urethane. 2. The predominant response to all three agents was a depression of neuronal firing rate. The responses to dopamine and amantadine could be antagonized by the dopamine receptor blocking agent, chlorpromazine. 3. Amantadine did not cause any potentiation of dopamine responses, suggesting that inhibition of amine uptake was not responsible for its effects. 4. The responses of pyramidal tract cells in the cerebral cortex to dopamine, amphetamine and amantadine were compared in control groups of rats and rats pretreated with reserpine (10 mg/kg i.p.) or alpha-methyl-p-tyrosine methyl ester (200 mg/kg i.p.). The reduction of cortical catecholamine concentrations was confirmed by a direct fluorimetric assay method. 5. Responses to dopamine were unaltered in the amine-depleted animals compared with controls. Responses to amantadine and amphetamine were reduced but not abolished. 6. It is concluded that amantadine acts partly by releasing catecholamines from neuronal stores. The residual responses to amantadine and amphetamine may be the result of a direct postsynaptic receptor stimulation.

Amantadine↗
PubMed1976

Blockade by amino acid antagonists of neuronal excitation mediated by the pyramidal tract.

1. The responses to glutamate and amino acid antagonists of cells in the cuneate nucleus of anaesthetized rats have been examined.2. 1-hydroxy-3-amino-pyrrolidone-2 (HA-966) and glutamic acid diethylester applied by micro-iontophoresis reduced glutamate excitation of the neurons. HA-966 WAS EFFECTIVE ON MORE CELLS THAN GLUTAMIC ACID DIETHYLESTER AND WAS MORE POTENT. HA-966 DID NOT AFFECT EXCITATORY RESPONSES TO ACETYLCHOLINE.3. Spike activity of cuneate cells was evoked by stimulating the cerebral cortex. Spikeswhich could be attributed to monosynaptic activation of the cells were studied. The pyramidal tract is the only corticofugal pathway known to be capable of short latency activation of dorsal column nucleus neurones.4. HA-966 reversibly blocked the evoked activity in twenty-eight (70%) of forty units in which monosynaptically evoked spikes were induced.5. The results raise the possibility that the neurotransmitter released by neurones of the pyramidal tract may be an excitatory amino acid.

Action Potentials↗
PubMed1975

Cyclic AMP and cyclic GMP may mediate opposite neuronal responses in the rat cerebral cortex.

Electrophysiologically identified pyramidal tract neurons in the rat cerebral cortex were tested with norepinephrine, acetylcholine, adenosine 3',5'-monophosphate (cyclic AMP), and guanosine 3',5'-monophosphate (cyclic GMP) applied by microiontophoresis. The neurons were usually inhibited by norepinephrine and cyclic AMP, but excited by acetylcholine and cyclic GMP. These opposing responses of pyramidal tract neurons to cyclic AMP and cyclic GMP suggests that these two nucleotides could function as reciprocal intracellular second messengers for norepinephrine and acetylcholine, respectively.

Acetylcholine↗