Normal serotonin uptake by blood platelets and brain synaptosomes but selective impairment of platelet serotonin storage in mice with Chediack-Higashi syndrome

The Chediack-Higashi syndrome (CHS) is an autosomal recessive disorder reported in man and in several animal species including the "beige mice" (bg/bg). Among several manifestations of this genetic trait, deficiency of secretable substances - including serotonin - normally stored in platelet dense granules is a characteristic feature. The animal model of Chediak-Higashi syndrome used in the present study provides a unique opportunity to compare the kinetics of serotonin (5-hydroxytryptamine, 5-HT) uptake in platelets and brain synaptosomes in conditions of selective reduction of 5HT concentration in the platelets. The kinetics of 5HT uptake, as measured in the present study, was normal in synaptosomes and platelets from the same animals. The lower intraplatelet 5HT levels in bg/bg animals as compared to normal synaptosomes levels in the presence of normal uptake offer an indirect proof that the 5HT defect described in the CHS is due to an impaired 5HT storage mechanism. This is supported by the observation that spontaneous release of 5HT was markedly increased in platelets from CH5 mice but was normal in synaptosomes from the same animals. Thus platelets are a reliable model to study 5HT uptake, but not 5HT storage and release in brain synaptosomes.     

Effect of 17β-estradiol on calcium response to phytohaemagglutinin in human lymphocytes

Pre-treatment of human lymphocytes with 17-estradiol diminishes the increase in concentration of cytosolic free calcium after stimulation with phytohaemagglutinin. The effect is dependent on 17-estradiol concentration and on the preincubation time. The effect is not due to an interaction between 17-estradiol and phytohaemagglutinin, but appears to be a consequence of the binding of the hormone to the cell surface. The effect is specific for 17-estradiol, since the isomer and other steroid hormones (progesterone, testosterone, diethylstilbestrol and 5-androstan), have no effect. Since the effect of the 17-estradiol can be suppressed by treatment of lymphocytes with ouabain, it appears that the effect of estradiol on the rise of cytosolic calcium induced by phytohaemagglutinin is mediated by the (Na, K)-ATPase.     

Physiologic target of the Air-1 trans-activator revealed by stable transfection assay

RJ 2.2.5 is a human B cell mutant, derived from Raji cells, which has lost expression of major histocompatibility complex (MHC) class II genes because of a defect in the AIR1 locus function. The MHC class II-positive phenotype can be restored by introducing an active AIR1 locus or its mouse equivalent, Air-1. An example of the latter is the H4 cell hybrid, derived by somatic cell fusion between RJ 2.2.5 and mouse class II-positive spleen cells. H4 contains a single mouse chromosome, autosome 16, in which the Air-1 locus maps, and an entire RJ 2.2.5-derived genome. In the present study we show that the physiologic target of the Air-1 locus product is contained within a limited HLA-DRA promoter sequence of 300 base pairs, encompassing the crucial Y, X, and W cis-acting elements. A plasmid construct, pDRA300neo, containing the HLA-DRA promoter sequence which drives the expression of the neomycin resistance gene, has been stably integrated in the genome of the H4 hybrid. Transfectants selected in the presence of G418 retain mouse chromosome 16 and express the DR genes. On the other hand, transfectants grown in a non-selective medium segregate mouse chromosome 16; this is accompanied by a loss of DRA gene expression and G418 resistance, although pDRA300neo is still integrated in the genome. These results offer scope for using this experimental model to clone the Air-1 gene in a straightforward way. Correspondence to: R. S. Accolla.     

Diazepam increases membrane fluidity of rat hippocampus synaptosomes

Diazepam in vitro produced a concentration-dependent increase of membrane fluidity in crude synaptic membranes from rat hippocampus, but not cerebellum. Similar effects were obtained with higher concentrations of Ro 15-1788 and PK 11195, while zopiclone was completely inactive. In vivo acute treatment with diazepam and Ro 15-1788 gave results similar to those in vitro. The specific benzodiazepine antagonist also significantly increased membrane fluidity and was not able to reverse diazepam's effect. The data are discussed in terms of a possible role of protein kinase inhibition by the drugs not mediated by the 'central' or 'peripheral' type of benzodiazepine receptors.     

Evidence of the existence of two different intraneuronal pools from which pharmacological agents can release serotonin

The effect of various drugs on the release of [³H]-serotonin from synaptosomes of reserpine-treated rats was compared with that obtained with synaptosomes of untreated animals.The increase in [³H]-serotonin release induced by d-fenfluramine was virtually abolished by reserpine; the effect of d-norfenfluramine, the main metabolite of fenfluramine, was instead enhanced in synaptosomes of reserpine treated animals. [³H]-serotonin release induced by l-isomers of fenfluramine or norfenfluramine was increased or not affected, respectively, after reserpine treatment.The effects of other drugs, known to activate serotonin mechanisms such as metachlorophenylpiperazine and quipazine, like d-norfenfluramine, were increased by the reserpine treatment.The present data show that [³H]-serotonin can be released by drugs from two pools with different sensitivity to reserpine. The reserpinized synaptosomes could provide useful information on the mechanisms of action of drugs acting on brain serotonin.     

Reduction in the number of serotonin receptors in the brainstem of morphine dependent rats: Relation to blockade of naloxone precipitated jumping by serotonin agonists

The effect of various drugs was studied on the naloxone-precipitated withdrawal syndrome of morphine-dependent rats. Quipazine and metachlorophenylpiperazine, two agents mimicking serotonin at central receptors, markedly lowered the frequency of jumping in abstinent rats; m-chlorophenylpiperazine significantly blocked diarrhea as well. Ptosis and diarrhea but not jumping were significantly reduced by clonidine. None of the withdrawal signs considered was significantly affected by propranolol or haloperidol. A significant reduction in the number of ³H-serotonin binding sites was found in the brainstem of morphine-dependent rats, but no change was observed in the number of serotonin receptors in the cortex. The hypothesis is proposed that in morphine dependent rats a central serotoninergic hypofunction, probably related to a decrease in the number of serotonin receptors in the brainstem, occurs as a consequence of persistent activation of central serotonin function by long-term treatment with morphine. This mechanism appears to play a major role in the compulsive jumping shown by morphine-dependent rats after naloxone injection. Alpha₂ adrenergic sites may play a role in the manifestation of other withdrawal signs examined in this study.     

Correction to: Synthesis,protonation constants and biological activity determination of amino acid–salicylaldehyde‑derived Schiff bases

Amino Acids - Unfortunately in the online published article, the name of compound “L-salicylidenealanine” was published with incorrect spelling in the section “Synthesis of...     

8,000 years of climate,vegetation, fire and land-use dynamics in the thermo-mediterranean vegetation belt of northern Sardinia (Italy)

Vegetation History and Archaeobotany - Knowledge about the vegetation history of Sardinia, the second largest island of the Mediterranean, is scanty. Here, we present a new sedimentary record...     

Spatial genetic patterns of Octopus vulgaris Mediterranean populations support the hypothesis of a transitional zone across the Siculo-Tunisian Strait

Hydrobiologia - Recent research hypothesised that the Siculo-Tunisian Strait might fit, at least for some species, the picture of a genetic transitional zone instead of a sharp genetic break...