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α 2 ‐Adrenoceptor‐Mediated Inhibition of Electrically Evoked [ 3 H]Noradrenaline Release from Chick Sympathetic Neurons: Role of Cyclic AMP
Author(s) -
Boehm Stefan,
Huck Sigismund,
Koth Gabriele,
Drobny Helmut,
Agneter Ernst,
Singer Ernst A.
Publication year - 1994
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 - 10.1046/j.1471-4159.1994.63010146.x
Subject(s) - adrenergic receptor , medicine , endocrinology , norepinephrine , sympathetic nervous system , sympathetic activity , beta adrenoceptor , chemistry , neuroscience , biophysics , receptor , biology , heart rate , dopamine , blood pressure
This study explores the role of cyclic AMP in electrically evoked [ 3 H]noradrenaline release and in the α 2 ‐adrenergic modulation of this release in chick sympathetic neurons. Along with an increase in stimulation‐evoked tritium overflow, applications of forskolin enhanced the formation of intracellular cyclic AMP. Both effects of forskolin were potentiated by the phosphodiesterase inhibitor 3‐isobutyl‐1‐methylxanthine. The forskolin‐induced increase in overflow was abolished by the Rp ‐diastereomer of cyclic AMP‐thioate, an antagonist at cyclic AMP‐dependent protein kinases, and 1,9‐dideoxy‐forskolin, an inactive analogue at adenylyl cyclase, had no effect on the evoked overflow. A 24‐h pretreatment with either cholera toxin or forskolin reduced the subsequent forskolin‐induced accumulation of cyclic AMP and inhibited the stimulation‐evoked release. Basal cyclic AMP production, however, remained unaltered after forskolin treatment and was enhanced after 24 h of cholera toxin exposure. The α 2 ‐adrenergic agonist bromoxidine did not affect the formation of cyclic AMP stimulated by forskolin but reduced electrically evoked release. However, effects of bromoxidine on 3 H overflow were attenuated by forskolin as well as by 8‐bromo‐cyclic AMP. Effects of bromoxidine on [ 3 H]noradrenaline release were paralleled by an inhibition of voltage‐activated Ca 2+ currents, primarily through a delayed time course of current activation. This effect was abolished when either forskolin or 8‐bromo‐cyclic AMP was included in the pipette solution. Both substances, however, failed to affect Ca 2+ currents in the absence of bromoxidine. These results suggest that the signaling cascade of the α 2 ‐adrenergic inhibition of noradrenaline release involves voltage‐activated Ca 2+ channels but not cyclic AMP. Elevated levels of cyclic AMP, however, antagonize this α 2 ‐adrenergic reduction, apparently through a disinhibition of Ca 2+ channels.