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Endogenous Noradrenaline Activates α 2 ‐Adrenoceptors on Serotonergic Nerve Endings in Human and Rat Neocortex
Author(s) -
Feuerstein T. J.,
Mutschler A.,
Lupp A.,
Velthoven V.,
Schlicker E.,
Göthert M.
Publication year - 1993
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1993.tb02148.x
Subject(s) - autoreceptor , idazoxan , rauwolscine , endocrinology , medicine , desipramine , phentolamine , serotonergic , neocortex , chemistry , prazosin , agonist , serotonin , methysergide , neurotransmitter , antagonist , stimulation , receptor , neuroscience , biology , antidepressant , hippocampus
Slices from human neocortex preincubated with [ 3 H]serotonin ([ 3 H]5‐HT) were superfused and stimulated electrically to investigate whether the α 2 ‐adrenoceptors on serotonergic terminals can be stimulated by endogenous noradrenaline (NA) released from neighboring noradrenergic fibers. The stimulation‐evoked 3 H overflow, representing action potential‐induced, exocytotic release of 5‐HT, was depressed by the NA uptake blocker (+)‐oxaprotiline. Rauwolscine (a mixed α 2 ‐adrenoceptor antagonist/5‐HT autoreceptor agonist) or phentolamine [a combined α‐ adrenoceptor/5‐HT autoreceptor antagonist; the latter drug in the presence of (+)‐oxaprotiline] enhanced the release when the 5‐HT autoreceptors had previously been blocked by metitepine. Under hypothermia the release of 5‐HT was found to be decreased and that of NA to be increased; under these conditions idazoxan (an α 2 ‐adrenoceptor antagonist) enhanced the release of 5‐HT. In neocortex slices from rats (+)‐oxaprotiline similarly depressed the release of 5‐HT (measured with the same methods) as in human tissue. When rats were pretreated with 6‐hydroxydopamine, the inhibitory effect of exogenous NA on 5‐HT release was increased, and in slices from rats pretreated with desipramine, it was decreased. In conclusion, α 2 ‐heteroreceptors can be activated by endogenous NA released from neighboring noradrenergic fibers. Because regulatory processes analogous to those in rats probably occur in humans as well, an up‐ or down‐regulation of α 2 ‐ heteroreceptors in depressed patients with a (pathological) decrease or a (therapeutic) enhancement of the noradrenergic neurotransmission may also be assumed to occur.