Beta₂-adrenoceptors as modulators of glial immune function

Abstract

The endogenous anti-inflammatory and neurotrophic effects of noradrenahne are mediated by β2-adrenoceptors on astrocytes and microglia in the central nervous system (CNS). Notably, clinical studies demonstrate that β2-adrenoceptors are absent from astrocytes of patients with Multiple Sclerosis (MS) and loss of glial β2- adrenoceptors is likely to contribute to the chronic inflammation observed in this disorder. Additionally it has been suggested that a loss of central noradrenergic tone may contribute to the development of Alzheimer’s disease by facilitating the chronic neuroinflammation and amyloid-P deposition which is characteristic of this disease. The biological basis for the loss of β2-adrenoceptors in MS is not known, therefore the possibility that exposure to an inflammatory stimulus could down-regulate glial β2-adrenoceptor expression and responsiveness was examined here. The results demonstrate that in vitro exposure of primary mixed glial cultures to LPS+lFN-y down-regulates β2-adrenoceptor mRNA and cell surface expression (~50%) and reduces the accumulation of intracellular cAMP in response to the β2-adrenoceptor agonist salbutamol, an effect found to be specific to β2- adrenoceptor and not due to an effect on intracellular signaling events.