Antagonists of GABA B receptors are expected to have proconvulsant acti on also in developing brain. Two antagonists (CGP55845 and CGP46381) were tested in a model of cortical epileptic afterdischarges (ADs) in 12-, 18- and 25-day-old rat pups with implanted electrodes. CGP55845 was dissolved in dimethylsulfoxide and the results demonstrated marked proconvulsant action of this solvent which masked possible action of the antagonist. Water soluble antagonist CGP46381 led to marked potentiation of ADs in 12-day-old animals, its action decreased with age, it was negligible in 25-day-old rats. Our results demonstrated important inhibitory role of GABA B receptors at very early stages of maturation., P. Mareš., and Obsahuje bibliografii a bibliografické odkazy
Matrix metalloproteinases (MMPs) is a family of proteolytic enzymes involved in remodeling of extracellular matrix. Although proteolytic enzymes are produced by many cell types, mast cells seem to be more important than other types in remodeling of pulmonary arteries during hypoxia. Therefore, we tested in vitro production of MMPs and serine proteases in four cell types (mast cells, fibroblasts, vascular smooth muscle cells and endothelial cells) cultivated for 48 h under normoxic or hypoxic (3 % O2) conditions. MMP-13 was visualized by immunohistochemistry, MMP-2 and MMP-9 were detected by zymography in cell lysates. Enzymatic activities (MMPs, tryptase and chymase) were estimated in the cultivation media. Hypoxia had a minimal effect on total MMP activity in the cultivation media of all types of cells, but immunofluorescence revealed higher intensity of MMP-13 in the cells exposed to hypoxia except of fibroblasts. Tryptase activity was three times higher and chymase activity twice higher in mast cells cultivated in hypoxia than in those cultured in normoxia. Among all cell types studied here, mast cells are the most abundant source of proteolytic enzymes under normoxic and hypoxic conditions. Moreover, in these cells hypoxia increases the production of both specific serine proteases tryptase and chymase, which can act as MMPs activators., H. Maxová ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Alterations in the intrinsic properties of Purkinje cells (PCs) may contribute to the abnormal motor performance observed in ataxic rats. To investigate whether su ch changes in the intrinsic neuronal excitability could be attributed to the role of Ca2+ -activated K+ channels (KCa ), whole cell current clamp recordings were made from PCs in cerebellar slices of control and ataxic rats. 3-AP induced profound alterations in the intrinsic properties of PCs, as evidenced by a significant increase in both the membrane input resistance and the initial discharge frequency, along with the disruption of the firing regularity. In control PCs, the blockade of small conductance KCa channels by UCL1684 resulted in a significant increase in the membrane input resistance, action potential (AP) half-width, time to peak of the AP and initial discharge frequency. SK channel blockade also significantly decreased the neur onal discharge regularity, the peak amplitude of the AP, the amplitude of the after-hyperpolarization and the spike fr equency adaptation ratio. In contrast, in ataxic rats, both the firing regularity and the initial firing frequency were significantly increased by the blockade of SK channels. In conclusion, ataxia may arise from alterations in the functional contribution of SK channels, to the intrinsic properties of PCs., M. Kaffashian ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy