Distribution of α2-adrenergic receptor subtype gene expression in rat brain

Mika Scheinin*, Jon W. Lomasney, Diane M. Hayden-Hixson, Uta B. Schambra, Marc G. Caron, Robert J. Lefkowitz, Robert T. Fremeau

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

356 Scopus citations

Abstract

α2-Adrenergic receptors in brain are important presynaptic modulators of central noradrenergic function (autoreceptors) and postsynaptic mediators of many of the widespread effects of catecholamines and related drugs. α2-Adrenergic agonists are currently used as antihypertensives and preanesthetic agents, but new subtype-selective α2-adrenoceptor agonists and antagonists have additional therapeutic application potential. Three genes encoding specific α2-adrenoceptor subtypes (α2A, α2B, and α2C) have been isolated and characterized. RNA blotting indicates that all three are expressed in rat brain. This study used in situ hybridization with 35S-labeled RNA probes to map the distribution of α2-adrenoceptor subtype gene expression in rat brain. α2A mRNA was most abundant in the locus coeruleus, but was also widely distributed in the brain stem, cerebral cortex, septum, hypothalamus, hippocampus and amygdala. α2B mRNA was observed only in the thalamus. α2C mRNA was mainly localized to the basal ganglia, olfactory tubercle, hippocampus, and cerebral cortex. These mRNA distributions largely agree with previous findings on the α2-adrenoceptor distributions in the rat brain, but suggest that the localization patterns for each receptor subtype are unique. The expression of α2A mRNA in noradrenergic neurons indicates that this subtype mediates presynaptic autoreceptor functions. Furthermore, the localization of α2A mRNA in noradrenergic projection areas suggests that this receptor may also have an important role in mediating postsynaptic effects. The precise physiological and pharmacological roles of the α2-adrenoceptor subtypes are still largely unknown, but it is expected that in situ hybridization coupled to various methods to identify the transmitter phenotypes of the subtype-expressing neurons will help to clarify these important issues in the near future.

Original languageEnglish (US)
Pages (from-to)133-149
Number of pages17
JournalMolecular Brain Research
Volume21
Issue number1-2
DOIs
StatePublished - Jan 1994

Keywords

  • Autoreceptor
  • Gene expression
  • In situ hybridization histochemistry
  • Locus coeruleus
  • Noradrenaline

ASJC Scopus subject areas

  • Molecular Biology
  • Cellular and Molecular Neuroscience

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