Histamine and Some Antihistamines: Their Actions on Cerebral Cortical Neurones

Phillis, John W.; Tebécis, A. K.; York, Donald H.

doi:10.1111/j.1476-5381.1968.tb00492.x

Cited by 80 publications

(27 citation statements)

References 28 publications

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“…This phenomenon might explain the absence of excited cells in the cerebral cortex of unanaesthetized decerebrate and N20-halothane anaesthetized cats (Crawford & Curtis, 1966;Phillis, Tebecis & York, 1968). These latter experiments used smaller braking currents (5-10 nA) and higher drug concentrations (1-1.5 M) than those presently employed.…”

Section: Monoamine Excitationmentioning

confidence: 68%

The responses of cortical neurones to monoamines under differing anaesthetic conditions

Johnson¹,

Roberts²,

Straughan³

1969

The Journal of Physiology

125

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SUMMARY1. Noradrenaline, isoprenaline, 5-hydroxytryptamine and acetylcholine have been applied into the environment of single neurones in the cat cerebral cortex by micro-iontophoresis. The influence of anaesthesia on the neuronal responses to these drugs was studied.2. In general, excitation of neurones by noradrenaline occurred commonly in both unanaesthetized encephale isole (48 %) and N20-halothane anaesthetized preparations (57 %) while depressions were less frequent (24 and 20 % respectively). The picture differed markedly in barbiturate anaesthetized animals where excitation was uncommon (12 %) and the majority of cells (59 %) was depressed by noradrenaline. Although fewer cells were studied, similar differences were obtained with isoprenaline and 5-hydroxytryptamine for the three types of preparation. In sharp contrast, the vast majority of cells was excited by acetylcholine in each of the preparations: encephale isole 84 %; N20-halothane 92 %; barbiturate anaesthetized preparations 85 %.3. The differing neuronal responses observed in these experimental situations were not the result of variations in the depth of anaesthesia.4. Although the depths at which neurones were encountered within the cortex did not differ in N20-halothane and encephale isole preparations, significantly more cells were found in deeper layers of cortex in barbiturate preparations. The proportion of cells excited or depressed by noradrenaline was generally similar at each depth in the three preparations used.5. The distribution of rates of cell firing was strikingly similar in each preparation, and most of the cells studied had frequencies below 10/sec. * Rothschild Fellow. IPhy. 203 9 E. S. JOHNSON AND OTHERS 6. The direction in which a cell responds to noradrenaline is mainly determined by the type of anaesthetic used, and not by the depth of anaesthesia, the rate of cell firing, or cell depth within the cortex. This suggests important differences in the central pharmacology of halothane and barbiturates.

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Section: Monoamine Excitationmentioning

confidence: 68%

The responses of cortical neurones to monoamines under differing anaesthetic conditions

Johnson¹,

Roberts²,

Straughan³

1969

The Journal of Physiology

125

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“…Specificity of strychnine antagonism It has been reported that strychnine applied to cortical neurones blocked the inhibitory actions of NA, 5-HT and ACh (Phillis & York, 1967) and histamine (Phillis et al, 1968 tions) have shown that NA, 5-HT and GABA equilibrium depressions were not antagonized by strychnine (25 nA). The apparent reduction of the responses they obtained resulted from the prolongation of the time-course of depression.…”

Section: -Hydroxytryptamine Depressionmentioning

confidence: 99%

“…In view of the reports that strychnine also prevents the depression of cortical neurones by acetylcholine (ACh), noradrenaline (NA), 5-hydroxytryptamine (5-HT) and histamine, by Phillis & York (1967) and Phillis, Tebecis & York (1968), the specificity of strychnine antagonism on cortical neurones must be questioned.…”

Section: Introductionmentioning

confidence: 99%

Amino‐acid induced depression of cortical neurones

Johnson

Roberts

Straughan

1970

British J Pharmacology

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Summary1. The effects of strychnine on the degree of depression of neuronal firing induced by glycine, y-aminobutyric acid (GABA) and 5-hydroxytryptamine (5-HT) have been examined quantitatively. All drugs were applied by iontophoresis to spontaneously active cerebral cortical neurones in the anaesthetized cat. The application of these drugs was continued until a plateau or equilibrium depression was reached. The time taken to reach this steady state was noted. Dose-response curves were then constructed for those currents giving less than complete depression. 2. Glycine was less potent than GABA and about 7-fold larger currents were needed to achieve comparable depression. 5-HT was also a weak depressant compared with GABA and had 06 the potency of glycine on a current basis. 3. Strychnine in currents up to 25 nA shifted the dose-response curve of glycine to the right at a time when equilibrium depression in the same cells induced by the control agonists GABA or 5-HT was unaffected. These currents of strychnine did, however, prolong the time-course of onset of GABA and 5-HT depression. 4. In larger currents strychnine reduced GABA equilibrium depression, but the dose-response curve was not shifted in a parallel fashion. 5. It is concluded that strychnine can specifically and competitively antagonize the effect of glycine on cortical neurones.

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“…All three analogues show considerable GABA-like activity on neurones in the mammalian central nervous system: iontophoretic application produces a marked inhibition in neuronal cell firing, and this can be antagonized by bicuculline, N-methyl bicuculline or picrotoxin. Furthermore they are resistant to the action of strychnine, suggesting that their effect resembles that of GABA rather than glycine (Kmjevic & Phillis, 1963;Phillis, Tebecis & York, 1968; Curtis, The effect of the analogues on GABA accumulation by isolated ganglia was determined by incubating ganglia in Krebs solution (1 ml/ganglion) containing 0.2 AM PHI-GABA ([PH-2-31-y-aminobutyric acid, 10 Ci/mmol, New England Nuclear) in the absence or presence of a 1 mM concentration of the analogues. Incubations were continued for 30 min at 25°C in the presence of 10 gM amino-oxyacetic acid to prevent GABA metabolism (Walsh, Bowery, Brown & Clark, 1974).…”

mentioning

confidence: 99%

A Comparison of Γ‐aminobutyric Acid and the Semi‐rigid Analogues 4‐aminotetrolic Acid, 4‐aminocrotonic Acid and Imidazole‐4‐acetic Acid on the Isolated Superior Cervical Ganglion of the Rat

Bowery

Jones

1976

British J Pharmacology

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The rat superior cervical ganglion possesses receptors for γ‐aminobutyric acid (GABA). This can be demonstrated in vitro by recording the changes in ganglionic surface potential which occur after the addition of GABA to the bathing solution. The actions of three conformationally‐restricted analogues of GABA namely 4‐aminotetrolic acid (4‐ATA), trans 4‐aminocrotonic acid (4‐ACA) and imidazole‐4‐acetic acid (IAA) have been examined for activity at this peripheral receptor. All three analogues depolarized the ganglion in a manner similar to GABA. Their actions were transient and were ‘occluded” by GABA; also the log dose‐response curve in each case was parallel to that of GABA. Molar potencies relative to GABA (=1) were 4‐ACA =1.48, IAA = 0.100, 4‐ATA = 0.0028. The action of each analogue could be blocked by the GABA antagonists bicuculline and tetramethylenedisulphotetramine at doses which had relatively little effect on responses to the cholinomimetic carbachol. 4‐ACA and IAA (1 mM) significantly reduced the ganglionic accumulation of [3H]‐GABA (0.2 μM) by 88% and 58% respectively whereas 4‐ATA (1 mM), caused no significant reduction in [3H]‐GABA accumulation.

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Histamine and Some Antihistamines: Their Actions on Cerebral Cortical Neurones

Cited by 80 publications

References 28 publications

The responses of cortical neurones to monoamines under differing anaesthetic conditions

The responses of cortical neurones to monoamines under differing anaesthetic conditions

Amino‐acid induced depression of cortical neurones

A Comparison of Γ‐aminobutyric Acid and the Semi‐rigid Analogues 4‐aminotetrolic Acid, 4‐aminocrotonic Acid and Imidazole‐4‐acetic Acid on the Isolated Superior Cervical Ganglion of the Rat

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