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F Van Huizen

Publications and source records attributed to F Van Huizen.

5 recordsLinked to original sources

Genomic organization, coding sequence and functional expression of human 5-HT2 and 5-HT1A receptor genes.

The family of serotonin receptors consists of at least eight distinct subtypes, divided into four classes based on their pharmacological and functional characteristics. Here we report the cloning and expression in Swiss 3T3 cells of the human 5-HT2 and 5-HT1A receptor subtypes. Both genes encode functional receptors for 5-HT, that differ considerably in genomic structure, primary amino acid sequence, pharmacology and signal transduction. The 5-HT1A receptor transfectants displayed a single high affinity site for the agonist [3H](+/-)-8-hydroxy-2-(di-n-propylamino)tetralin HBr ([3H]8-OH-DPAT) and a pharmacological profile specific for the 5-HT1A receptor. In these transfectants, 5-HT mediated a dose-dependent inhibition of forskolin-stimulated cAMP levels. Cells expressing the 5-HT2 receptor exhibited high affinity binding for the antagonist [3H]ketanserin with a 5-HT2 receptor specific pharmacological profile. In these cells 5-HT activated phospholipase C in a dose-dependent manner. The 5-HT2 receptor displayed a genomic organization quite different from the 5-HT1A, 5-HT1B and 5-HT1D receptor subtypes. While these receptors are encoded by one single exon, the 5-HT2 receptor is encoded by three exons separated by two introns. The latter finding adds and additional molecular criterion for receptor classification.

3T3 Cells↗

Sodium channel toxins veratrine and veratridine modify opioid and muscarinic but not beta-adrenergic binding sites in brain slices.

We have examined the influence of the sodium channel toxins veratrine and veratridine on mu-opioid ([3H]-DAGO), muscarinic ([3H] NMS) and beta-adrenergic ([3H] CGP) receptors in rat brain slices. These drugs reduce opioid and muscarinic binding while leaving beta-receptors unaffected. Veratrine is inhibitory at 0 degree or at 30 degrees C whereas veratridine is without effect at 0 degree C. These data suggest that some factor contained in the mixture of drugs (veratrine) can block opioid and muscarinic receptors independently of depolarization. Veratridine does not affect muscarinic receptors at ice temperature. Similar observations were made in thin sections of cat brain at 0 degree C. The concentrations of the toxins which cause 50% inhibition of binding are well within the range (5 x 10(-5) M-10(-4) M) routinely used for depolarization experiments. We suggest that caution be used in the interpretation of results obtained from veratrum alkaloid-induced depolarizations. It would not be surprising if the binding of other ligands to their receptors was also affected.

Animals↗

Tetrodotoxin enhances initial neurite outgrowth from fetal rat cerebral cortex cells in vitro.

The effect of two different concentrations of the sodium channel blocker tetrodotoxin on neurite outgrowth from fetal rat cerebral cortex neurons was studied in vitro. A concentration of 10(-6) M tetrodotoxin enhanced after two days in vitro: the percentage of isolated cells and reaggregates which formed neurites, the number of neurites per cell soma, and neurite elongation and subsequent branching. The effects observed after treatment with 10(-7) M tetrodotoxin were on the whole intermediate between control and 10(-6) M tetrodotoxin.

Animals↗

Spontaneous neuronal firing patterns in fetal rat cortical networks during development in vitro: a quantitative analysis.

The development of spontaneous bioelectric activity (SBA) was studied in dissociated occipital cortex cultures prepared from 19 day old rat fetuses. All cultures, recorded one per diem from 5 to 33 days in vitro (div), showed SBA. Computer analysis of 76 extracellularly recorded single unit spike trains was carried out after selection on the basis of stationarity criteria. Statistically significant developmental trends were found in (i) interspike interval dependencies and (ii) fluctuations in mean firing rate, on the order of a minute or longer. The highly dependent firing patterns, including stereotyped bursting, were present mostly in the 9-12 div group, whereas minute-to-minute fluctuations in the intensity of firing were considerably more pronounced in the oldest group (22-33 div) than in the younger cultures. In addition, firing categories defined on the basis of factor-analysis revealed that such fluctuations were almost exclusively to be found in neurons which fired in a pronounced 'burst', rather than a relatively continuous fashion. Only a few mature appearing synaptic structures were observed electron microscopically prior to 12 div, but increased steadily in number thereafter. No cultures prior to 14 div, but all cultures older than this, stained positively for the presence of glutamic acid decarboxylase. An extensive immunoreactive, putative GABAergic, network was present by three weeks in vitro.

Action Potentials↗