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The effects of low concentrations of toluene (40-80 ppm, 3 days, 6 h/day) were investigated on spontaneous and on apomorphine-induced locomotor activity in the rat, and were correlated to effects on S(-)[N-propyl-3H(N)]-propylnorapomorphine ([3H]NPA) binding in rat neostriatal membranes, on membrane fluidity, membrane leakage, and calcium levels in synaptosomes from the frontoparietal cortex, the neostriatum and the subcortical limbic area, and on serum hormone levels. Toluene exposure (80 ppm, post-exposure delay 18 h) alone did not affect locomotor activity, but attenuated apomorphine-induced (0.05 mg/kg, s.c.) suppression of rearing, and potentiated apomorphine-induced (1 mg/kg, s.c.) increases in locomotion and rearing. Toluene exposure increased the KD value of [3H]NPA binding without affecting the Bmax. All these effects were absent at 40 ppm of toluene or at a post-exposure delay of 42 h. Toluene exposure (80 ppm, post-exposure delay of 18 h) did not affect the serum levels of prolactin, TSH, corticosterone, or aldosterone, or synaptosomal membrane fluidity and calcium levels, whereas membrane leakage was increased in the neostriatum. The present study indicates that the reduction of D-2 receptor affinity by short-term, low-dose toluene exposure is accompanied by a reduced D-2 autoreceptor function and an enhanced postsynaptic D-2 receptor function.

The effects of exposure to ganglioside GM1 and to toluene in vitro upon synaptosomal integrity have been examined using fluorescence polarization of two probes: 1-[4(trimethylamino)phenyl]-1,3,5-hexatriene (TMA-DPH) and 1,6-diphenyl-1,3,5-hexatriene (DPH) to measure membrane anisotropy, and the fluorescent indicator fura-2 to assay levels of cytosolic calcium [( Ca2+]i). The anisotropy of both TMA-DPH and DPH was decreased by toluene, implying increased membrane fluidity. The decrease in TMA-DPH but not in DPH anisotropy was prevented by pretreatment with GM1 in concentrations as low as 10 microM. This is not an additive interaction since 10 microM of GM1 alone did not significantly modulate TMA-DPH anisotropy. When the GM1 treatment succeeded the addition of toluene the decrease in anisotropy of both probes was reversed. Toluene treatment increased [Ca2+]i in a dose- and time-dependent manner. This increase could partially be both prevented and reversed by treatment with 50 microM of GM1. These effects may reflect an additive interaction, since this concentration of GM1 alone reduced [Ca2+]i. The present results show that toluene increases membrane fluidity and intracellular calcium levels. These effects may be counteracted by the endogenous compound GM1.

The nucleus tractus solitarii (NTS) in the dorsomedial medulla comprises a wide range of neuropeptides and biogenic amines. Several of them are related to mechanisms of central blood pressure control. Angiotensin II (Ang II), neuropeptide Y (NPY) and noradrenaline (NA) are found in the NTS cells, as well as their receptors. Based on this observation we have evaluated the modulatory effect of these peptide receptors on a2-adrenoceptors in the NTS. Using quantitative receptor radioautography, we observed that NPY and Ang II receptors decreased the affinity of a2-adrenoceptors for their agonists in the NTS of the rat. Cardiovascular experiments agreed with the in vitro data. Coinjection of a threshold dose of Ang II or of the NPY agonists together with an ED50 dose of adrenergic agonists such as NA, adrenaline and clonidine counteracted the depressor effect produced by the a2-agonist in the NTS. The results provide evidence for the existence of an antagonistic interaction between Ang II at1 receptors and NPY receptor subtypes with the a2-adrenoceptors in the NTS. This receptor interaction may reduce the transduction over the a2-adrenoceptors which can be important in central cardiovascular regulation and in the development of hypertension

The actions of fibroblast growth factors (FGFs), particularly the basic form (bFGF), have been described in a large number of cells and include mitogenicity, angiogenicity and wound repair. The present review discusses the presence of the bFGF protein and messenger RNA as well as the presence of the FGF receptor messenger RNA in the rodent brain by means of semiquantitative radioactive in situ hybridization in combination with immunohistochemistry. Chemical and mechanical injuries to the brain trigger a reduction in neurotransmitter synthesis and neuronal death which are accompanied by astroglial reaction. The altered synthesis of bFGF following brain lesions or stimulation was analyzed. Lesions of the central nervous system trigger bFGF gene expression by neurons and/or activated astrocytes, depending on the type of lesion and time post-manipulation. The changes in bFGF messenger RNA are frequently accompanied by a subsequent increase of bFGF immunoreactivity in astrocytes in the lesioned pathway. The reactive astrocytes and injured neurons synthesize increased amount of bFGF, which may act as a paracrine/autocrine factor, protecting neurons from death and also stimulating neuronal plasticity and tissue repair