Ivermectin acts as a positive allosteric regulator of several ligand gated channels including the glutamate-gated chloride channel (GluCl), γ-aminobutyric acid type-A receptor, glycine receptor, neuronal α 7-nicotinic receptor and purinergic P2X4 receptor. In most of the ivermect in-sensitive channe ls, the effects of ivermectin include the potentiation of agonist-induced currents at low concentrations and channel opening at higher concentrations. Based on mutagenesis, electrophysiological recordings and functional an alysis of chimeras between ivermectin-sensitive and ivermectin-insensitive receptors, it has been concluded that ivermectin acts by insertion between transmembrane helices. The three-dimensional structure of C. elegans GluCl complexed with ivermectin has revealed the details of the ivermectin-binding site, however, no generic motif of amino acids could accurately predict ivermectin binding site for other ligand gated channels. Here, we will review what is currently known about ivermectin binding and modulation of Cys-loop receptor family of ligand-gated ion channels and what are the critical structur al determinants underlying potentiation of the P2X4 receptor channel., H. Zemkova ... [et al.]., and Obsahuje bibliografii a bibliografické odkazy
Allostery is an essential property of many physiological mechanisms. Cooperativity together with allostery is observed in the behavior of multisubunit receptors. Here we summarize and compare several approaches to the description and analysis of allosteric phenomena with emphasis on the receptors connected to ionic channels as a model. Several simplified methods are discussed in comparison with the microscopic kinetic scheme, affinity-efficacy separation and a thermodynamic approach.
The aim of the experiment was to investigate the mechanism of harmful alloxan action in vivo. 75 mg/kg b.w. of this diabetogenic agent were administered to fasting rats. Two minutes later the animals were decapitated. It was observed that alloxan caused a distinct rise in blood insulin and glucose levels with a concomitant drop of free fatty acids. The amount of sulfhydryl groups in the liver of alloxan-treated rats was decreased and glutathione peroxidase activity was substantially higher. These results indicate that some changes observed in alloxan-induced diabetes can not only be the consequence of B cells damage by alloxan but may also be the result of its direct influence on other tissues. It was also observed that glucose given 20 min before alloxan injection only partially protected against the deleterious effects of alloxan.
We consider a non-consuming agent investing in a stock and a money market interested in the portfolio market price far in the future. We derive a strategy which is almost log-optimal in the long run in the presence of small proportional transaction costs for the case when the rate of return and the volatility of the stock market price are bounded It\^o processes with bounded coefficients and when the volatility is bounded away from zero.
Beside Antonín Švehla, it was - without question - Alois Rašín, who influenced the process of the coup the most. His vision of the coup was not dull, simple or technological; it was a perfectly prepared and managed action, which was also to be enjoyed by its participants. In the centre of Rašín's thoughts were the preparations of the law drafts (also called The Founding Law of the State and above all The First Law), which should have given a legal framework to the new state. A coup that did not get out of hand and which was, once completed, immediately sealed by a law was his ideal but attainable vision. Rašín was probably the only one who tried to prepare such a law. No other proposal is known. All of this attests to his capabilities as statesman and his ability to act. and Článek zahrnuje odkazy pod čarou