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C Hammond

Publications and source records attributed to C Hammond.

104 records · Page 6Linked to original sources

Pharmacological properties of acetylcholine-induced excitation of subthalamic nucleus neurones.

1. In 15 rats anaesthetized with ketamine, microiontophoretically applied acetylcholine (ACh) excited all 58 cells studied in the subthalamic nucleus (STN). 2. The ACh-evoked excitation was slow in onset and outlasted the ACh application. There was no sign of desensitization when the ACh application was prolonged or repeated. The excitation was prolonged by a concomitant application of physostigmine. 3. Acetyl-beta-methyl choline and oxotremorine were effective cholinomimetics. Nicotine had no effect. 4. The ACh excitation was antagonized by stropine and scopolamine but not by mecamylamine. 5. It was condluded that STN ACh receptors are muscarinic in character. 6. Since large microiontophoretic applications of Mg2+ did not suppress ACh-evoked excitation, it is suggested that ACh acts postsynaptically. 7. The excitatory response of STN cells to striatal or pallidal stimulation was unaffected by atropine administered either microiontophoretically to single cells or intravenously (3 mg/kg) to the whole animal.

Acetylcholine↗

Electrophysiological demonstration of an excitatory subthalamonigral pathway in the rat.

The subthalamonigral projection was studied with extracellular techniques in the rat. Orthodromic and antidromic stimulations of this pathway were performed in different sets of experiments in order to exclude the possible activation of passing fibers. A majority of the recorded cells in the subthalamic nucleus (STN) were antidromically activated by nigral stimulation. It was furthermore shown that the subthalamofugal fibers are excitatory to cells located in the pars compacta as well as in the pars reticulata of the substantia nigra. The possible existence of another descending STN pathway is also discussed.

Animals↗

Electrophysiological properties of identified output neurons of the rat substantia nigra (pars compacta and pars reticulata): evidences for the existence of branched neurons.

In Ketamine-anaesthetized rats the nigral efferents to the ipsilateral striatum, to both VL/VM thalamic nuclei and to both superior colliculi were studied. Nigral output neurons were antidromically activated from these target nuclei and characterized by their spontaneous activity and cellular localization within the substantia nigra. Neurons in the pars compacta, which give rise to the dopaminergic nigro-striatal pathway, exhibited a low spontaneous discharg rate (3 to 6/sec) and their axon had a slow conduction velocity (0.33 to 1 m/sec). They were antidromically activated from the striatum only. Neurons in the pars reticulata were characterized by a higher spontaneous activity (20 to 40/sec) anda faster conduction velocity (1.9 m/sec to 10 m/sec). They were antidromically activated from the thalamus, superior colliculus and striatum. Furthermore, some of these neurons were found to have branching axons projecting at least to two of the different target nuclei studied.

Animals↗

Relationship between the transport of iron and the amount of specific colicin Ia membrane receptors in Escherichia coli.

Strains of Escherichia coli K-12 defective in their ability to utilize exogenously supplied iron due to genetic defects in the entF, tonB, fes, or fep gene exhibited elevated levels of the specific outer-membrane receptor for colicin Ia when compared with parental strains. Although entF, fes, and fep strains showed a higher degree of Ia sensitivity than did the parental strains, tonB strains were resistant to colicin action. The colicin insensitivity of tonB strains was not due to hyperproduction of enterochelin. Growth in medium containing 101.8 muM Fe2+ led to a lowering of receptor levels in all the above strains and resulted in decreased colicin Ia sensitivity in all strains except tonB, which was already at maximal resistance. Growth in citrate plus iron (1.8 muM) or in ferrichrome resulted in a substantial reduction in both receptor levels and Ia sensitivity in ent, fes, and fep strains but had no effect on receptor levels in tonB strains. Growth in citrate did not lead to an alteration in receptor levels in a mutant specifically defective in citrate-mediated iron transport. The presence of enterochelin during growth led to a reduction in the number of receptors in the parental and ent strains but not in tonB, fes, or fep strains. Thus, in all cases examined, there was an inverse relationship between the number of colicin receptors per cell and the ability of the strain to take up iron from the growth medium. This suggests that under conditions of iron limitation there is a derepression of colicin Ia receptor biosynthesis. These results may point to a role of the colicin I receptor in iron uptake.

Binding Sites↗

A phenothiazine derivative in the treatment of spasticity.

The efficacy of a selective fusimotor suppressant, the phenothiazine (+/-)-10-3-dimethylamino-2-methylpropyl)-2-valeroylphenothiazine, has been assessed in a double-blind crossover trail in eight patients suffering from cerebral spasticity and one patient suffering from spinal spasticity. Dosage was 40 mg daily. Independent clinical and electromyographic methods of assessment were used. The active agent produced a small but significant reduction in spasticity, although this was of clinical value in only a few patients. There were few side-effects. It is recommended that further studies using higher dosages be undertaken.

Brain Injuries↗

cGMP-dependent protein kinase enhances Ca2+ current and potentiates the serotonin-induced Ca2+ current increase in snail neurones.

Protein phosphorylation catalysed by cyclic AMP-dependent, Ca2+/calmodulin-dependent and Ca2+/diacylglycerol-dependent protein kinases is important both in the modulation of synaptic transmission and in the regulation of neuronal membrane permeability (for reviews see refs 5-7). However, there has previously been no evidence for the involvement of cyclic GMP-dependent protein kinase (cGMP-PK) in the regulation of neuronal function. Serotonin induces an increase of Ca2+ current in a group of identified ventral neurones of the snail Helix aspersa. This effect is probably mediated by cGMP because it is mimicked by the intracellular injection of cGMP or the application of zaprinast, an inhibitor of cGMP-dependent phosphodiesterase. We have now found that the effect of either serotonin or zaprinast on the Ca2+ current is potentiated by the intracellular injection of cGMP-PK. Moreover, the intracellular injection of activated cGMP-PK (cGMP-PK + 1 microM cGMP) greatly enhances the Ca2+ current of the identified ventral neurones seen in the absence of serotonin. These results indicate that cGMP-PK has a physiological role in the control of the membrane permeability of these neurones.

Action Potentials↗

Cholecystokinin induces a decrease in Ca2+ current in snail neurons that appears to be mediated by protein kinase C.

Three distinct classes of protein kinases have been shown to regulate Ca2+ current in excitable tissues. Cyclic AMP-dependent protein kinase mediates the action of noradrenaline on the Ca2+ current of cardiac muscle cells. Cyclic GMP-dependent protein kinase mediates the serotonin-induced modulation of the Ca2+ current in identified snail neurons. The Ca2+/diacylglycerol-dependent protein kinase (protein kinase C) has also been found to regulate Ca2+ currents of neurons. However, no neurotransmitter has yet been shown to regulate Ca2+ current through the activation of protein kinase C. We now report that cholecystokinin, a widely occurring neuropeptide which is present in molluscan neuron, modulates the Ca2+ current in identified neurons of the snail Helix aspersa, and that this effect appears to be mediated by protein kinase C. Specifically, sulphated cholecystokinin octapeptide 26-33 (CCK8), activators of protein kinase C, and intracellular injection of protein kinase C, all shorten the Ca2+-dependent action potential and decrease the amplitude of the Ca2+ current in these cells. All these effects are not reversible within the duration of the experiments. Moreover, intracellular injections of low concentrations of protein kinase C, which are ineffective by themselves, enhance the effectiveness of low concentrations of CCK8 on the Ca2+ current.

Animals↗

Vibration sense and tarsal disintegration.

The extent of loss of vibration and pressure sensations was assessed in 21 leprosy patients with disintegration of the tarsus. Feet which had and did not have tarsal disintegration both showed severe impairment of pressure sensation, but the loss of vibration sense was more severe in feet which had undergone the destructive process. It appears that loss of deep sensation is an important factor in the process of tarsal disintegration in feet which are already anaesthetic. Measurement of vibration sense using a biosthesiometer may be a valuable clinical test in the investigation and follow-up of the patient with the insensitive foot to identify those at risk of developing tarsal disintegration.

Adult↗