caa a22 4500 469079401 CHVBK 20180323132945.0 cr unu---uuuuu 170328e19920401xx s 000 0 eng 10.1007/BF00176617 doi (NATIONALLICENCE)springer-10.1007/BF00176617 Estimation of the biophase concentration of noradrenaline at presynaptic α2-adrenoceptors in brain slices [Elektronische Daten] [Clemens Allgaier, Ernst Agneter, Thomas Feuerstein, Ernst Singer] Summary: The aim of the present study was to determine the local concentrations of noradrenaline existing at presynaptic α2-adrenoceptors during electrical pulse train stimulation of brain slices at different frequencies. The experiments are based on the assumption that the concentration of released noradrenaline at the α2-adrenoceptors exerting a certain autoinhibition should be equal to the concentration of exogenous noradrenaline causing the same inhibition under conditions in which any influence of the released transmitter is excluded. In order to avoid autoinhibition, hippocampus and cortex slices of the rabbit and the rat, prelabelled with [3H]noradrenaline and superfused in presence of an uptake inhibitor, were electrically stimulated using 4 pulses delivered at 100 Hz (POP stimulation). Exogenous noradrenaline diminished the overflow of tritium elicited by POP stimulation in a concentration-dependent manner. In rabbit brain tissues the EC50 value and maximum inhibition of noradrenaline release were found to be approximately 6 nmol/l and more than 95%, respectively, whereas in rat tissues the corresponding values were between 20 and 30 nmol/l and approximately 90%. When electrical stimulation was performed with trains of 36 pulses delivered at 0.1, 0.3 or 3 Hz in absence or presence of an uptake inhibitor, the α2-adrenoceptor antagonist yohimbine (1 or 10 μmol/l) enhanced the evoked tritium overflow in a manner which was dependent on the frequency of stimulation and on blockade of the re-uptake mechanism. The facilitatory effects of yohimbine reflected an extent of autoinhibition which was between 53% (36 pulses/0.1 Hz, no uptake inhibitor) and 85% (36 pulses/3 Hz, uptake inhibitor present) in rabbit and between 16% (36 pulses/0.3 Hz, no uptake inhibitor) and 71% (36 pulses/3 Hz, uptake inhibitor present) in rat brain slices. Accordingly, the corresponding estimated biophase concentrations of noradrenaline were generally higher in rat than in rabbit tissues (they were between 32.5 and 74.5 or 5.1 and 51.6 nmol/l in the presence or absence of an uptake inhibitor, respectively, in the rat, and between 15 and 23.1 or 6.1 and 18.6 nmol/l in the rabbit). The observed frequency dependence of the effect of re-uptake blockade on the calculated biophase concentrations of noradrenaline would be compatible with the idea of a dependence of the effectiveness of the re-uptake mechanism on the firing rate of the neurone in being more effective at lower frequencies. Moreover, the stikingly low biophase concentrations of noradrenaline suggest that also in brain tissue noradrenaline causes lateral inhibition of release as has recently been shown for guinea-pig vas deferens. Springer-Verlag, 1992 Noradrenaline release nationallicence Presynaptic α2-adrenoceptors nationallicence Biophase concentration of noradrenaline nationallicence Rabbit hippocampus and cortex nationallicence Rat hippocampus and cortex nationallicence Allgaier Clemens Institute of Pharmacology and Toxicology, University of Freiburg, Hermann-Herder-Strasse 5, W-7800, Freiburg i.Br., Germany aut Agneter Ernst Institute of Pharmacology, University of Vienna, Währingerstrasse 13A, A-1090, Wien, Austria aut Feuerstein Thomas Neuropharmakologisches Labor der Neurologischen Universitätsklinik, c/o Gödecke AG, Mooswaldallee 1-9, W-7800, Freiburg i.Br., Germany aut Singer Ernst Institute of Pharmacology, University of Vienna, Währingerstrasse 13A, A-1090, Wien, Austria aut Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/4(1992-04-01), 402-409 0028-1298 345:4<402 1992 345 210 https://doi.org/10.1007/BF00176617 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/BF00176617 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Allgaier Clemens Institute of Pharmacology and Toxicology, University of Freiburg, Hermann-Herder-Strasse 5, W-7800, Freiburg i.Br., Germany aut NATIONALLICENCE 700 1- Agneter Ernst Institute of Pharmacology, University of Vienna, Währingerstrasse 13A, A-1090, Wien, Austria aut NATIONALLICENCE 700 1- Feuerstein Thomas Neuropharmakologisches Labor der Neurologischen Universitätsklinik, c/o Gödecke AG, Mooswaldallee 1-9, W-7800, Freiburg i.Br., Germany aut NATIONALLICENCE 700 1- Singer Ernst Institute of Pharmacology, University of Vienna, Währingerstrasse 13A, A-1090, Wien, Austria aut NATIONALLICENCE 773 0- Naunyn-Schmiedeberg's Archives of Pharmacology Springer-Verlag 345/4(1992-04-01), 402-409 0028-1298 345:4<402 1992 345 210 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer