PRESYNAPTIC NORADRENERGIC ALPHA-RECEPTORS AND MODULATION OF H-3-NORADRENALINE RELEASE FROM RAT-BRAIN SYNAPTOSOMES

The depolarization (15 mM K+)-induced release of 3H-NA from superfused rat brain synaptosomes and the effects of α-noradrenergic drugs thereon were studied. Noradrenalin (NA; in the presence of the uptake inhibitor desipramine) reduced synaptosomal 3H-NA release. Reduction of the concentration of calcium ions in the medium during K+ stimulation greatly enhanced the sensitivity of 3H-NA release to α-receptor-mediated inhibition. Under these conditons NA dose-dependently inhibited 3H-NA release from synaptosomes obtained from cortex or hypothalamus, but did not affect 3H-NA release from striatal (i.e. dopaminergic) synaptosomes. Adrenaline, clonidine and oxymetazoline potently inhibited 3H-NA release from cortex synaptosomes at concentrations in the nanomolar range. Phentolamine by itself did not affect synaptosomal 3H-NA release, but antagonized the inhibitory effects of both noradrenaline and andrenaline. The data obtained further substantiate the hypothesis that the α-receptors mediating a local negative feedback control of NA release are localized on the varicosities of central noradrenergic neurons.Furthermore, noradrenergic nerve terminals in the hypothalamus appear to be less sensitive to α-receptor-mediated presynaptic inhibition than those in the cortex. © 1979.