Publications by authors named "Newberry N"

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1. Human alpha 7 nicotinic acetylcholine (ACh) receptors were expressed in Xenopus oocytes and the effects of the N-methyl-D-aspartate (NMDA) receptor open channel blockers memantine and cerestat on this receptor were examined using two-electrode voltage-clamp recordings and 125I-alpha-bungarotoxin (125I-alpha-bgtx) binding. 2.

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We have used intracellular recording techniques to examine the effects of 5-hydroxytryptamine (5-HT, serotonin) on 5-HT-containing neurones of the guinea pig dorsal raphe nucleus in vitro. Bath-applied 5-HT (30-300 microM) had two opposing effects on the membrane excitability of these cells, reflecting the activation of distinct 5-HT receptor subtypes. As demonstrated previously in the rat, 5-HT evoked a hyperpolarization and inhibition of 5-HT neurones, which appeared to involve the activation of an inwardly rectifying K(+) conductance.

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Chlormethiazole has sedative, hypnotic, anticonvulsant and neuroprotective properties. Using in vitro grease-gap recordings, we show that it inhibits epileptiform activity in neocortical slices superfused with Mg(2+)-free medium (IC(50) approximately 200 microM). At an antiepileptic concentration (300 microM), chlormethiazole potentiated the action of exogenously applied GABA (1 mM) but did not affect responses to the glutamate receptor agonists N-methyl-D-aspartate (10 microM) or L-quisqualic acid (3 microM).

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Depolarising GABA(A) receptor-mediated responses recorded from the optic nerve using a grease gap technique were modulated by classical potentiators of GABA(A) receptors. The benzodiazepine, chlordiazepoxide, the barbiturate, pentobarbitone and the widely used anaesthetic, propofol, all potentiated gamma-aminobutyric acid (GABA) responses. They did so with different maximal efficacies, propofol>pentobarbitone>chlordiazepoxide, and potencies on the basis of EC(50) estimates, chlordiazepoxide>propofol>pentobarbitone.

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Using intracellular recordings, we have studied the action of 5-hydroxytryptamine (5-HT) on slices of human temporal, occipital and frontal cortex maintained in vitro. The recordings were usually made 1.2 to 1.

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We have studied the effects of single and repeated electroconvulsive shock (ECS) treatment on the mRNA levels of several glutamate receptors in the dentate gyrus and CA1 regions of the rat brain. In the dentate gyrus, such treatment elevated the mRNAs for the NMDA subunits NR2A and NR2B, but it reduced the mRNA for the metabotropic glutamate receptor mGlu5b. With the exception of NR2A, this effect was specific to the dentate gyrus.

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We have developed an in vitro model of spreading depression (SD) in rat neocortex. KCl application induced a propagating wave of SD associated with a change of optical lucency and an extracellular negative wave. Both of these were abolished by aminophosphonovaleric acid (100 microM), indicating SD's mediation by NMDA receptors.

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Brain-derived neurotrophic factor (BDNF) (20 ng/ml) significantly enhanced the growth of the somata of GABA-immunoreactive neurones in primary cultures of hippocampal neurones from postnatal rats after only 24h. Whole-cell patch-clamp experiments showed an increase in spontaneous synaptic activity between neurones with time in culture. After 10 days in culture, 90% of neurones sampled in control cultures showed spontaneous synaptic activity, whereas in cultures treated with BDNF, 100% of neurones had synaptic inputs after only 6 days.

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Stable transfection of the human neuroblastoma cell line SH-SY5Y with the human 5-hydroxytryptamine2A (5-HT2A) or 5-HT2C receptor cDNA produced cell lines demonstrating ligand affinities that correlated closely with those for the corresponding endogenous receptors in human frontal cortex and choroid plexus, respectively. Stimulation of the recombinant receptors by 5-HT induced phosphoinositide hydrolysis with higher potency but lower efficacy at the 5-HT2C receptor (pEC50 = 7.80 +/- 0.

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There are no published data for the activity of technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) found in breast milk. The amount of radioactivity in breast milk following the administration of 500 MBq 99mTc-HMPAO for a brain perfusion study has been measured. The effective dose to the infant was calculated to be 0.

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Primers for 5-HT2A, 5-HT2B and 5-HT2C receptor mRNAs were used in reverse transcriptase-linked polymerase chain reactions (RT-PCR) to determine the presence of these transcripts in the guinea pig superior cervical ganglion. This was done to help identify an as yet unknown 5-HT2-like receptor which, in addition to 5-HT2A receptors, mediates a slow depolarization of this preparation. PCR products corresponding to 5-HT2A and 5-HT2B, but not 5-HT2C, receptor mRNA could readily be detected.

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Here we report the existence of burst-firing neurones in the rat dorsal raphe as detected in vivo using intracellular electrophysiological techniques. These neurones discharged single action potentials and doublets or triplets of action potentials in a slow and regular pattern. The apparent input resistance, action potential width and firing threshold of these burst-firing raphe neurones were indistinguishable from classical 5-HT neurones.

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1. Using the whole-cell variation of the patch-clamp technique to record from mammalian NG108-15 cells, we have studied the ligand-gated ion channel current activated by a high concentration (100 microM) of local pressure-applied 5-hydroxytryptamine (5-HT). The response was induced at intervals of at least 90-120 s, which allowed the receptor to fully recover between activations.

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1. We have studied the pharmacology of the depolarization by 5-hydroxytryptamine (5-HT) of the guinea-pig isolated superior cervical ganglion (SCG) using the grease-gap technique. We studied the effects of selective and non-selective antagonists on the responses to 5-HT and other 5-HT receptor agonists.

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We have investigated the identity and intracellular cascade of responses resulting from activation of the endogenous 5-hydroxytryptamine receptor in the C6 rat glioma cell line. Sequence analysis of reverse transcription-polymerase chain reaction products derived from C6 glioma cell messenger RNA revealed complete homology with a portion of the rat 5-hydroxytryptamine2A receptor. The binding of [3H]ketanserin to cell membranes demonstrated a significant correlation with the 5-hydroxytryptamine2A receptor in rat frontal cortex.

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1. We have studied three hypoxia-induced phenomena in the CA1 stratum pyramidale of the rat hippocampal slice: (a) the increase in extracellular potassium ion concentration ([K+]e) measured with ion-sensitive microelectrodes, (b) the intracellularly-recorded pyramidal cell hyperpolarization and (c) the extracellularly-recorded depression of the synaptically-evoked field potential recorded in stratum pyramidale. 2.

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N-[2-[4-(2-methoxyphenyl)-1-piperazinyl]ethyl]-N-(2- pyridinyl)cyclohexanecarboxamide trihydrochloride (WAY-100635) is a potent and selective 5-HT1A receptor antagonist in a slice preparation of the guinea pig dorsal raphe nucleus: the inhibitory actions on 5-HT neuronal firing of 5-hydroxytryptamine (5-HT, serotonin), 5-carboxamidotryptamine (5-CT) and 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), but not those of baclofen, were abolished by 30 nM WAY-100635. The selective 5-HT1D receptor antagonist N-[4-methoxy-3-(4-methyl-1-piperazinyl)phenyl]-2'- methyl-4'-(5-methyl-1,2,4-oxadiazol-3-yl) [1,1-biphenyl]-4-carboxamide (GR127935, 300 nM) did not attenuate the 5-HT induced inhibition, indicating that 5-HT1D receptors do not contribute to the inhibitory action of exogenous 5-HT on 5-HT neurones.

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The C6 glioma cell line possesses 5-HT2A receptors that have been shown to increase intracellular calcium levels. We have studied the electrophysiological response of these cells to 5-HT using the whole-cell recording method. Under voltage-clamp, 5-hydroxytryptamine (5-HT) produced an outward current in these cells which was inhibited by extracellularly applied ketanserin and spiperone and by EGTA (10 mM) in the recording electrode.

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The effect of a novel 5-HT3 receptor antagonist, BRL 46470, has been studied on two electrophysiological models for 5-HT3 receptors: grease-gap recordings from rat isolated vagus nerve and whole-cell patch-clamp recordings from mouse neuroblastoma-rat glioma NG108-15 cells. Its action on the rat vagus nerve was compared to that of four other 5-HT3 receptor antagonists. On the rat vagus, BRL 46470 reduced the maximum depolarizing response to 5-HT in a concentration-dependent manner with an IC50 of 0.

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The interaction of the enantiomers of mianserin with the 5-HT3 receptor was determined. Using [3H]granisetron binding, (-)-mianserin was more potent than (+)-mianserin (pKi 8.46 and 6.

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Grease-gap recordings revealed that 5-hydroxytryptamine (5-HT) depolarized the ferret vagus nerve (pEC50 = 4.9). This response was mimicked by 2-methyl-5-HT and 1-phenylbiguanide, but not by 5-carboxamidotryptamine.

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The action of a novel 5-HT3 receptor antagonist, AS-5370, has been studied on two electrophysiological models for 5-HT3 receptors: whole-cell patch-clamp recordings from mouse neuroblastoma-rat glioma (NG108-15) cells and grease-gap recordings from rat isolated vagus nerve. The 5-hydroxytryptamine (5-HT)-induced fast inward current of voltage-clamped NG108-15 cells was antagonized by 1 nM AS-5370 in an insurmountable manner. On the rat vagus, AS-5370 reduced the maximum depolarizing response to 5-HT in a concentration-dependent manner.

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