Induction of the vesicular monoamine transporter by elevated potassium concentration in cultures of rat sympathetic neurons.
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.
Desnos
C
C
U.A. C.N.R.S. de Neurobiologie Physico-Chimique, Institut de Biologie Physico-Chimique, Paris, France.
Raynaud
B
B
Vidal
S
S
Weber
M J
MJ
Scherman
D
D
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
D015306:Biogenic Monoamines; D002352:Carrier Proteins; C032811:dihydrotetrabenazine; D004299:Dopamine beta-Hydroxylase; D011188:Potassium; D004298:Dopamine; D013747:Tetrabenazine