Existence of functional beta1- and beta2-adrenergic receptors on microglia.

We examined the expression and function of beta-adrenergic receptor (beta-AR) subtypes in both isolated primary rat microglia and a rat microglial cell line. RT-PCR analyses revealed that microglia expressed beta(1)- and beta(2)-ARs but not beta(3)-ARs, whereas rat primary peritoneal macrophages expressed only beta(2)-ARs. Stimulation of beta-ARs on microglia by norepinephrine (NE) resulted in an increase in the level of intracellular cAMP and the subsequent expression of interleukin-1beta mRNA. These effects were prevented by propranolol. Similar results were obtained with other selective beta(1)-AR agonists and antagonists. beta(2)-ARs on microglia were also functional. It is possible that noradrenergic innervations participate in the control of microglial functions via beta(1)-ARs on microglia in the brain, because NE has high affinity for beta(1)- and beta(3)-ARs but little or no affinity for beta(2)-ARs. It seems physiologically significant that microglia can be controlled by NE, which predominates over epinephrine in the brain, whereas macrophages in peripheral tissues can be controlled by epinephrine, which is at higher levels in peripheral tissues.