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Estimation of the biophase concentration of noradrenaline at presynaptic alpha 2-adrenoceptors in brain slices.

Author information

1
Institute of Pharmacology and Toxicology, University of Freiburg, Federal Republic of Germany.

Abstract

The aim of the present study was to determine the local concentrations of noradrenaline existing at presynaptic alpha 2-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 alpha 2-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 alpha 2-adrenoceptor antagonist yohimbine (1 or 10 mumol/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.(ABSTRACT TRUNCATED AT 250 WORDS).

PMID:
1320208
[Indexed for MEDLINE]

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