title: Sodium dependent 3H-noradrenaline release from rat neocortical slices in the absence of extracellular calcium: presynaptic modulation by mu-opioid receptor and adenylate cyclase activation.
abstract: In Ca2+-free EGTA (1 mmol/l)-containing medium veratrine (3 mumol/l) and ouabain (100 mumol/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 mumol/l). These effects of veratrine and ouabain were virtually additive and independent of whether the noradrenaline uptake carrier was blocked with 1 mumol/l desipramine or not. The adenylate cyclase activator forskolin (10 nmol/l - 10 mumol/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 mu-opioid receptor agonist [D-Ala, MePhe4, Gly-ol5]enkaphalin (DAGO, 3 nmol/l - 1 mumol/l) in a concentration-dependent manner. The inhibitory effects of 1 mumol/l DAGO were abolished by 1 mumol/l naloxone. On the other hand, preincubation of the slices for 1 h with the delta-opioid receptor-selective irreversible ligand fentanyl isothiocyanate (1 mumol/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 mu-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.
authors.affiliation: Department of Pharmacology, Free University, Medical Faculty, Amsterdam, The Netherlands.
authors.forename: A N
authors.initials: AN
authors.lastname: Schoffelmeer
authors.forename: F
authors.initials: F
authors.lastname: Hogenboom
authors.forename: A H
authors.initials: AH
authors.lastname: Mulder
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000502:physiology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D004789:Enzyme Activation; D005110:Extracellular Space / Q000378:metabolism; D008297:Male; D009638:Norepinephrine / Q000378:metabolism*; D010042:Ouabain / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000502:physiology*; D012964:Sodium / Q000502:physiology*; D014702:Veratrine / Q000494:pharmacology*
chemical_list: D004745:Enkephalins; D011957:Receptors, Opioid; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D005576:Colforsin; D010042:Ouabain; D012964:Sodium; D000262:Adenylyl Cyclases; D014702:Veratrine; D002118:Calcium; D003891:Desipramine; D009638:Norepinephrine