Sodium dependent 3H-noradrenaline release from rat neocortical slices in the absence of extracellular calcium presynaptic modulation by μ-opioid receptor and adenylate cyclase activation
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In Ca2+-free EGTA (1 mmol/l)-containing medium veratrine (3 μmol/l) and ouabain (100 μmol/l) strongly enhanced the efflux of 3H-noradrenaline from superfused rat brain neocortical slices prelabelled with the radioactive amine. In both cases 3H-noradrenaline release was prevented by tetrodotoxin (1 μmol/l). These effects of veratrine and ouabain were virtually additive and independent of whether the noradrenaline uptake carrier was blocked with 1 μmol/l desipramine or not. The adenylate cyclase activator forskolin (10 nmol/l–10 μmol/l) strongly enhanced veratrine- and ouabain-induced 3H-noradrenaline release, without affecting spontaneous tritium efflux. The release induced by both stimuli was profoundly inhibited by the selective μ-opioid receptor agonist [d-Ala, MePhe4, Gly-ol5]enkaphalin (DAGO, 3 nmol/l–1 μmol/l) in a concentration-dependent manner. The inhibitory effects of 1 μmol/l DAGO were abolished by 1 μmol/l naloxone. On the other hand, preincubation of the slices for 1 h with the δ-opioid receptor-selective irreversible ligand fentanyl isothiocyanate (1 pmol/l) did not change the inhibitory effects of DAGO.
These data show that veratrine- and ouabain-induced 3H-noradrenaline release from central noradrenergic nerve terminals is facilitated by increasing intracellular cyclic AMP levels and reduced by activation of presynaptic μ-opioid receptors, indicating the involvement of exocytotic neurotransmitter release. The results provide further evidence for the hypothesis that under these conditions neurotransmitter release from central noradrenergic neurons is triggerred by a Na+-induced efflux of Ca2+ ions from intracellular stores.
Key words3H-noradrenaline release Veratrine Ouabain Intracellular calcium μ-Opioid receptor Cyclic AMP
[d-Ala2, McPhe4, Gly-ol5]enkephalin
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