Antidepresszáns vegyületek nem konvencionális hatásai: receptor ioncsatornák modifikációjának vizsgálata az ionáramok kinetikai elemzésével = Unconventional effects of antidepressants: Modification of receptor ion channel function studied by kinetic analysis of ionic currents

Hippokampális sejtek natív ioncsatornáin különböző monoamin visszavétel gátló vegyületek hatását vizsgáltuk. Terápiás koncentrációtartományon belül (IC50 10 microM) GABAA és AMPA receptorok esetében. A nátriumcsatornák esetében új mechanizmusát írtuk le a használatfüggő gátlásnak. Kimutattuk, hogy a desipramine és a fluoxetine ezzel az új mechanizmussal gátolja a nátriumcsatornákat: elsődleges hatásuk a lassú inaktivált állapot stabilizálása. Feltételezzük, hogy ez a hatás befolyásolhatja a neuronok integratív működését. Káliumcsatornák esetében a fluoxetine gátolja a „delayed rectifier”, és a „slow transient” áramokat, de nem módosítja a „fast transient” áramokat. A slow transient áramok gátlása feltételezésünk szerint az extracelluláris oldalról ható csatorna-blokk mechanizmussal történik. NMDA receptorok esetében kimutattuk, hogy a desipramine és a fluoxetine hasonló koncentrációban gátolja a receptorok által közvetített áramokat, a gátlás mechanizmusa azonban gyökeresen eltér. Míg a desipramine feszültségfüggő módon, csatorna-blokk mechanizmussal gátol, és kötőhelye valószínűleg a pórus belsejében található, a fluoxetine gátlása nem feszültségfüggő, és valószínűleg extracelluláris kötőhelye van. | We studied the effect of monoamine reuptake inhibitors on native ion channels of hippocampal neurons. Within the therapeutical concentration range (IC50 10 microM) GABAA and AMPA receptors were also affected. We have identified a novel mechanism of use-dependent sodium channel inhibition using the dopamine reuptake blocker GBR 12909. We have proven that the antidepressants desipramine and fluoxetine causes inhibition of sodium channels by this novel mechanism: stabilization of slow inactivated conformation. We suppose that inhibition by this mechanism may affect the integrative function of neurons. Fluoxetine inhibited delayed rectifier and slow transient types of potassium channels, while not affecting fast transient channels. Inhibition of slow transient channels is probably due to ion channel block mechanism with extracellular access to the binding site. Desipramine and fluoxetine inhibited NMDA receptors with similar potency, but by a fundamentally different mechanism. While desipramine causes a voltage-dependent inhibition by a channel block mechanism having its binding site within the pore, the inhibition by fluoxetine is voltage-independent, with a binding site located extracellularly

Property management of some agricultural companies in south great plain region

As it is a well-known fact, the capital requirement of agriculture is high. In addition, its suitability for quick change of activity is significantly limited. The share of agriculture in total investment was remarkably smaller than its contribution to gross domestic product, especially in the nineties. According to a study of Central Statistical Office in 2008 the value of the cancelled investments approaches 129 million Euros from which almost 80% is the loss of the three dominantly agricultural regions (South Great Plain, North Great Plain, and South Transdanubia). Due to the cancelled developments the technical level of agricultural property did not improve significantly contributing to the decrease of the economic significance of the sector. Moreover, the usage of outdated machines and equipment reduces the competitiveness of agriculture. During the investigation 265 questionnaires were filled in mostly by large-scale agricultural companies in South Great Plain and some of them were interviewed as well. The examination of existing capacities and technologies showed that 60% of the firms have a medium-term plan and 70% of them have an investment plan. This is extremely positive, although most of the investments are based on loans and subsidies. This kind of attitude indicates a certain level of ability for taking risk. In most of the cases the examined investment means technology improvement as well, machinery and building investments were carried out characteristically from subsidies. Developing their own breeds and innovation are generally not typical in the sector, but according to our data their proportion has been increasing. It is interesting that there is not any significant difference between small-scale and largescale enterprises in connection with innovation activity that is smaller firms at least as innovative as bigger ones