Presynaptic α2-adrenoceptors control excitatory, but not inhibitory, transmission at rat hippocampal synapses

摘要: The effects of noradrenaline on neurotransmission at rat hippocampal synapses were investigated by recording autaptic currents in single neurons isolated glial microislands. Noradrenaline reduced excitatory, but not inhibitory, a pertussis toxin-sensitive manner, the amine did affect glutamate-evoked currents. The inhibition excitatory was half-maximal 0.11 ± 0.06 μm. α2-adrenoceptor agonists UK 14304 and clonidine equipotent to reducing these currents, whereas α1-adrenoceptor agonist methoxamine β-adrenoceptor isoprenaline (isoproterenol) ineffective. reduction altered α1-adrenergic antagonist urapidil or β-antagonist propranolol, α2-antagonist yohimbine. subtype-preferring antagonists rauwolscine phentolamine (both 0.3 μm) caused 9-fold 36-fold rightward shifts concentration-response curve for noradrenaline-dependent respectively. Prazosine (1 this curve. Noradrenaline voltage-activated Ca2+ microisland neurons. For comparison, GABAB baclofen both inhibitory diminished types 0.17 0.05 μm, 14 304 currents. noradrenaline-induced antagonized yohimbine, propranolol; α2-adrenergic displayed following rank order activity: > prazosine. Noradrenaline K+ failed alter frequency miniature postsynaptic measured mass cultures neurons. These results show that regulates transmission glutamatergic, GABAergic, via presynaptic α2-adrenoceptors α2A/D subtype. This action involves an no modulation spontaneous vesicle exocytosis currents. The formation receives dense noradrenergic innervation which originates primarily locus coeruleus (Loy et al. 1980), storage release preparations has been detail (Verhage 1992). Moreover, within hippocampus express receptors noradrenaline, i.e. adrenoceptors, including α1-, α2- β-subtypes, significant levels (Nicholas 1996). Nevertheless, actions remain controversial, ranging from excitation. Inhibitory reported include phenomena. (i) may cause hyperpolarizations pyramidal neurons, effect accompanied decrease potentials (Segal, 1981; Madison & Nicoll, 1986). (ii) facilitates γ-aminobutyric acid (GABA; Pittaluga Raiteri, 1987). (iii) catecholamine reduces site (Scanziani 1993) inhibits glutamate (Kamisaki (iv) Endogenous suggested be involved (Andreasen Lambert, 1991). On other hand, number have detected formation. found depolarize (Madison 1986) reduce 1988), presumably decreasing onto interneurons (Doze In brain regions, such as cerebellum, also exert contrasting augmentation well (Dolphin, 1982) facilitation evoked (Kondo Marty, 1998). contrast diverging obtained different vitro preparations, vivo, appears mainly neurotransmitter, since biogenic exerts antiepileptic activity (Chauvel Trottier, 1986). The present study performed re-evaluate focused particularly amine. To identify specific either GABAergic glutamatergic microislands cells used; form exclusively themselves, autapses (Bekkers Stevens, Such are ideally suited investigate function neurotransmitter separated each (Boehm Betz, 1997).