Galanin inhibits tyrosine hydroxylase expression in midbrain dopaminergic neurons

Scott E. Counts, Susan O. McGuire, Caryl E. Sortwell, Jacqueline Crawley, Timothy J. Collier, Elliott J. Mufson

Research output: Contribution to journalArticle

28 Scopus citations

Abstract

Galanin (GAL) inhibits midbrain dopamine (DA) activity in several experimental paradigms, yet the mechanism underlying this inhibition is unclear. We examined the effects of GAL on the expression of tyrosine hydroxylase (TH) in primary cultures of rat embryonic (E14) ventral mesencephalon (VM). One micromolar GAL had no effect on the number of TH-immunoreactive (ir) neurons in VM cultures. However, 1 μM GAL reduced an approximately 100% increase in TH-ir neurons in 1 mM dibutyryl cAMP (dbcAMP)-treated cultures by ∼50%. TH-ir neuron number in dbcAMP-treated VM cultures was dose-responsive to GAL and the GAL receptor antagonist M40 blocked GAL effects. Semi-quantitative RT-PCR and quantitative immunoblotting experiments revealed that GAL had no effect on TH mRNA levels in VM cultures but reduced TH protein. VM cultures expressed GALR1, GALR2, and GALR3 receptor mRNA. However, dbcAMP treatment resulted in a specific ∼200% increase in GALR1 mRNA. GALR1 activity is linked to a pertussis toxin (PTX)-sensitive opening of G protein-gated K+ channels (GIRKs). GAL reduction of TH-ir neuron number in dbcAMP + GAL-treated cultures was sensitive to both PTX and tertiapin, a GIRK inhibitor. GAL inhibition of midbrain DA activity may involve a GALR1-mediated reduction of th in midbrain dopaminergic neurons.

Original languageEnglish (US)
Pages (from-to)442-451
Number of pages10
JournalJournal of Neurochemistry
Volume83
Issue number2
DOIs
StatePublished - Oct 2002
Externally publishedYes

Keywords

  • Dopamine
  • Galanin
  • Substantia nigra
  • Tyrosine hydroxylase
  • Ventral tegmental area

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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