DISTRIBUTION OF ALPHA(2)-ADRENERGIC RECEPTOR SUBTYPE GENE-EXPRESSION IN RAT-BRAIN

alpha(2)-Adrenergic receptors in brain are important presynaptic modul ators of central noradrenergic function (autoreceptors) and postsynapt ic mediators of many of the widespread effects of catecholamines and r elated drugs. alpha(2)-Adrenergic agonists are currently used as antih ypertensives and preanesthetic agents, but new subtype-selective alpha (2)-adrenoceptor agonists and antagonists have additional therapeutic application potential. Three genes encoding specific alpha(2)-adrenoce ptor subtypes (alpha(2A), alpha(2B), alpha(2C)) have been isolated and characterized. RNA blotting indicates that all three are expressed in rat brain. This study used in situ hybridization with S-35-labeled RN A probes to map the distribution of alpha(2)-adrenoceptor subtype gene expression in rat brain. alpha(2A) mRNA was most abundant in the locu s coeruleus, but was also widely distributed in the brain stem, cerebr al cortex, septum, hypothalamus, hippocampus and amygdala.alpha(2B) mR NA was observed only in the thalamus. alpha(2C) mRNA was mainly locali zed to the basal ganglia, olfactory tubercle, hippocampus, and cerebra l cortex. These mRNA distributions largely agree with previous finding s on the alpha(2)-adrenoceptor distributions in the rat brain, but sug gest that the localization patterns for each receptor subtype are uniq ue. The expression of alpha(2A) mRNA in noradrenergic neurons indicate s that this subtype mediates presynaptic autoreceptor functions. Furth ermore, the localization of alpha(2A) mRNA in noradrenergic projection areas suggests that this receptor may also have an important role in mediating postsynaptic effects. The precise physiological and pharmaco logical roles of the alpha(2)-adrenoceptor subtypes are still largely unknown, but it is expected that in situ hybridization coupled to vari ous methods to identify the transmitter phenotypes of the subtype-expr essing neurons will help to clarify these important issues in the near future.