Histamine H3-receptor activation inhibits dopamine synthesis in rat striatum

Neuroreport. 2000 Jan 17;11(1):163-6. doi: 10.1097/00001756-200001170-00032.

Abstract

Unilateral 6-hydroxydopamine lesion to rat substantia nigra pars compacta resulted in a modest, but significant, decrease in the specific binding of N-alpha-[methyl-3H]histamine (19 +/- 5% reduction) to synaptosomal membranes from ipsilateral striata. Dopamine synthesis was assessed in striatal slices by determining [3H]DOPA accumulation after inhibition of DOPA decarboxylase. [3H]DOPA synthesis induced by 50 mM K+ (151 +/- 4% of basal) was prevented by either Ca2+ removal or by Ni2+. Depolarization-stimulated [3H]DOPA accumulation was reduced by the selective H3-agonist immepip (100 nM; 68 +/- 7% inhibition). The effect of immepip was reversed by thioperamide (100 nM), a selective H3-antagonist. Taken together, our results indicate that histamine modulates striatal dopamine synthesis by acting at H3-receptors located on dopaminergic nerve terminals.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dihydroxyphenylalanine / metabolism
  • Dopamine / biosynthesis*
  • Histamine Agonists / pharmacology*
  • In Vitro Techniques
  • Male
  • Methylhistamines / pharmacology
  • Neostriatum / drug effects
  • Neostriatum / metabolism*
  • Neurotransmitter Agents / metabolism
  • Oxidopamine / toxicity
  • Potassium / pharmacology
  • Radioligand Assay
  • Rats
  • Rats, Wistar
  • Receptors, Histamine H3 / drug effects*
  • Substantia Nigra / drug effects
  • Substantia Nigra / physiology
  • Sympatholytics / toxicity
  • Synaptosomes / drug effects
  • Synaptosomes / metabolism
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • Histamine Agonists
  • Methylhistamines
  • Neurotransmitter Agents
  • Receptors, Histamine H3
  • Sympatholytics
  • Dihydroxyphenylalanine
  • alpha-methylhistamine
  • Oxidopamine
  • Tyrosine 3-Monooxygenase
  • Potassium
  • Dopamine