title: Induction of the vesicular monoamine transporter by elevated potassium concentration in cultures of rat sympathetic neurons.
abstract: The expression of the vesicular monoamine transporter was studied in newborn rat sympathetic neurons and compared to that of the catecholamine biosynthesis enzymes tyrosine hydroxylase and dopamine-beta-hydroxylase. The vesicular monoamine transporter was assayed using the specific ligand [3H]dihydrotetrabenazine. In cultures grown for 10 days in the presence of 35 mM K+, tyrosine hydroxylase activity and the density of [3H]dihydrotetrabenazine binding sites were increased by a similar 2-3-fold factor, while dopamine-beta-hydroxylase activity and protein level were unchanged. Under these conditions, choline acetyltransferase activity was depressed by 90%. The induction of the vesicular monoamine transporter by high K+ was dependent upon Ca2+ entry through slow calcium channels since it was inhibited by the diphenylbutylpiperidine antagonist fluspirilene and by 20 mM Mg2+, and was enhanced by the dihydropyridine agonist, Bay K8644. The induction of the vesicular monoamine transporter by neuronal depolarization indicates the existence of a Ca2(+)-dependent mechanism of coregulation for this intrinsic component of monoaminergic synaptic vesicles and tyrosine hydroxylase. On the other hand, the apparent absence of dopamine-beta-hydroxylase induction is probably due to the continuous secretion of this intravesicular enzyme by the depolarized sympathetic neurons, an effect already observed in trans-synaptically stimulated adult sympathetic ganglion and adrenal medulla.
authors.affiliation: U.A. C.N.R.S. de Neurobiologie Physico-Chimique, Institut de Biologie Physico-Chimique, Paris, France.
authors.forename: C
authors.initials: C
authors.lastname: Desnos
authors.forename: B
authors.initials: B
authors.lastname: Raynaud
authors.forename: S
authors.initials: S
authors.lastname: Vidal
authors.forename: M J
authors.initials: MJ
authors.lastname: Weber
authors.forename: D
authors.initials: D
authors.lastname: Scherman
mesh_terms: D000818:Animals; D015306:Biogenic Monoamines / Q000493:pharmacokinetics*; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D004298:Dopamine / Q000378:metabolism / Q000493:pharmacokinetics; D004299:Dopamine beta-Hydroxylase / Q000378:metabolism*; D005728:Ganglia, Sympathetic / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000502:physiology*; D051381:Rats; D013572:Synaptic Vesicles / Q000378:metabolism*; D013747:Tetrabenazine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D015306:Biogenic Monoamines; D002352:Carrier Proteins; C032811:dihydrotetrabenazine; D004299:Dopamine beta-Hydroxylase; D011188:Potassium; D004298:Dopamine; D013747:Tetrabenazine