Subtype-specificity of the presynaptic α2-adrenoceptors modulating hippocampal norepinephrine release in rat

摘要: In vivo brain microdialysis and high-performance liquid chromatography with electrochemical detection were used to study the effect of different selective α2-antagonists on hippocampal norepinephrine (NE) release in freely moving awake rat. Systemic administration (0.5 mg/kg i.p.) either α2AD-antagonist BRL 44408 or α-2BC-antagonist ARC 239 did not significantly change basal NE. At a higher dose (5 was still ineffective, whereas caused significant increase extracellular level Similar results obtained from vitro perfusion experiments. Rat slices loaded [3H]NE electrical stimulation-evoked determined. The applied concentration range 10−8 10−6 M. increased electrically induced [3H]NE. agreement data displaced [3H]yohimbine cortical membranes rat high affinity less effective. pKi values eight α2-adrenergic compounds showed very good correlation (r = 0.98, slope 1.11 P < 0.0001) hippocampus frontal cortex where α2-adrenoceptors have been characterized as α2D-subtype. Our indicate that NE is regulated by α2D-adrenoceptors, species variation human α2A-subtype.