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Biomedical subjects

M A Simmonds

Publications and source records attributed to M A Simmonds.

At least 91 records · Page 5Linked to original sources
PubMed1973

A method for comparing the potencies of -aminobutyric acid antagonists on single cortical neurones using micro-iontophoretic techniques.

1. By the use of micro-iontophoretic techniques, quantitative estimates of the depressant effect of gamma-aminobutyric acid (GABA) have been obtained from single neurones in the middle suprasylvian gyrus of cat cerebral cortex.2. The progressive reduction in firing rate of the neurone during each microiontophoretic application of GABA was followed until inhibition was complete. The resultant time-response curves represented cumulative concentration-response relationships which could be characterized by measuring the time taken to achieve 50% inhibition (T50) of neuronal firing.3. The time-response curves for GABA could be displaced along the time axis by micro-iontophoretic application of picrotoxin, bicuculline or strychnine. A displaced curve was more nearly parallel to the control curve when responses were plotted against linear rather than log time.4. Picrotoxin usually increased T50 values for GABA, bicuculline could both increase and decrease them and strychnine usually decreased them.5. When displacements of GABA response curves were expressed as difference between T50 (test-control)/T50 (control), the values obtained were minimally influenced by the size of the current applying GABA and were unaffected by changes in the retaining current passed through the GABA barrel between applications.6. The use of this method to compare the micro-iontophoretic potencies of different GABA antagonists is discussed.

Aminobutyrates↗
PubMed1973

Microiontophoretic release of drugs from micropipettes: use of 24Na as a model.

1. The use of (24)Na(+) of high specific activity allowed its iontophoretic release from multibarrelled glass micropipettes to be followed over short periods with low currents.2. When a negative retaining current was passed to reduce diffusional efflux between the periods of positive current expulsion of (24)Na(+), the rate of release of (24)Na(+) during the expulsion period progressively increased during the first minute before becoming constant.3. The currents employed were similar to those normally used to regulate the microiontophoretic release of potent drugs such as gamma-aminobutyric acid. It is therefore concluded that, during the usual period of response to such drugs, the rate of release of drug is not constant but increasing.4. The implications of these observations for the construction of microiontophoretic dose-response relationships is discussed.

Animals↗
PubMed1973

A comparative study of some convulsant substances as gamma-aminobutyric acid antagonists in the feline cerebral cortex.

1. By the use of microiontophoretic techniques, quantitative estimates were obtained of the depressant effects of gamma-aminobutyric acid (GABA) on single feline cortical neurones.2. Picrotoxin, bicuculline, strychnine, (+)-tubocurarine, penicillin and leptazol were also applied microiontophoretically to single neurones. Sequential GABA applications were made before, during and after the microiontophoresis of these substances and any effects on the time course of the GABA depression were measured as an estimate of antagonism or potentiation of GABA.3. (+)-Tubocurarine was found to be a potent GABA antagonist. Picrotoxin and bicuculline were rather less potent and strychnine and penicillin only weakly active as GABA antagonists. Leptazol appeared to be inactive against GABA depressions.4. In addition, bicuculline and strychnine were found to be capable of potentiating the depressant action of GABA. This property was not shared by the other substances studied.5. All the substances studied produced changes in neuronal firing rate that did not correlate with GABA antagonism.6. In conclusion, several potent convulsants have been shown to be capable of GABA antagonism. It is not yet clear that this effect, rather than a direct effect on neuronal excitability, is the prime mechanism behind their convulsant properties.

Action Potentials↗
PubMed1972

Antagonism of GABA by picrotoxin in the feline cerebral cortex.

Picrotoxin and gamma-aminobutyric acid (GABA) were applied by microiontophoresis to an unselected population of neurones in the feline cerebral cortex. Picrotoxin was shown to antagonize the depressant effects of GABA and in addition appeared free of some of the actions of bicuculline which tend to mask GABA antagonism.

Action Potentials↗
PubMed1971

Inhibition by atropine of the increased turnover of noradrenaline in the hypothalamus of rats exposed to cold.

1. Small doses of (-)-[(3)H] noradrenaline were injected into the lateral cerebral ventricles in rats to label radioactively the endogenous noradrenaline (NA) stores.2. Intraventricular injection of 25 mug atropine methonitrate at the same time inhibited the increased rate of disappearance of [(3)H] NA from the hypothalamus at an environmental temperature of 9 degrees C, when compared with the values at 24 degrees C, without impairing temperature regulation.3. At 32 degrees C, 25 mug atropine methonitrate caused a lethal hyperthermia. A dose of 5 mug was not lethal and did not inhibit the increased rate of disappearance of [(3)H] NA from the hypothalamus.4. It is concluded that the pathway which stimulates an increased turnover of NA in the cold contains an atropine sensitive synapse but is not the principal pathway of heat production. The increased turnover of NA in the heat probably does not involve an atropine sensitive synapse.

Animals↗
PubMed1971

Differences in the uptake, storage and metabolism of (+)- and (-)-noradrenaline.

1. The rate of uptake of (+)- and (-)-noradrenaline was measured in isolated perfused hearts of reserpine treated rats, mice and guinea-pigs by fluorimetric analysis of the removal of catecholamine from the perfusion medium. In rat and mouse heart (-)-noradrenaline was taken up significantly more rapidly than (+)-noradrenaline, but no stereochemical specificity was found for noradrenaline uptake in guinea-pig hearts.2. Using radioactively labelled (+)-(14)C-noradrenaline and (-)-(3)H-noradrenaline, the kinetic constants for uptake into noradrenaline-containing and dopamine-containing synaptosomes from rat brain were determined. The uptake by noradrenaline terminals in the hypothalamus had a higher affinity for (-)-noradrenaline than for the (+)-isomer, but no differences in affinity were found for uptake into dopamine terminals.3. When equal amounts of labelled (+)- and (-)-noradrenaline were injected in vivo in double isotope experiments, the (+)-isomer disappeared more rapidly than the (-)-isomer from rat heart and spleen, but no significant differences were found between the rates of disappearance of the two isomers from rat brain or in the whole mouse.4. Analysis of the radioactive metabolites of the two isomers of noradrenaline after administration of mixed doses of the labelled substances showed that a significantly higher proportion of (+)-noradrenaline was metabolized to normetanephrine than of (-)-noradrenaline, in the whole mouse, rat heart and rat brain.

Animals↗