Chapter 13 - Signaling Pathway of β-Adrenergic Receptor in Astrocytes and its Relevance to Brain Edema

Abstract

Astroglia express β1- and β2-adrenergic receptors. Stimulation of astrocytic β1-adreneergic receptors induces extracellular regulated kinase 1 and 2 (ERK1/2) phosphorylation via protein kinase A, Gs/Gi switching, Ca2+ release from intracellular stores, metalloproteinase-catalyzed release of growth factor, and transactivation of epidermal growth factor receptor; while stimulation of β2-adrenergic receptors induces ERK1/2 phosphorylation by β-arrestin-mediated Src activation, without the involvement of epidermal growth factor receptor activation. Brain edema after 3h of focal ischemia followed by 8h reperfusion can be prevented by antagonists of β1-adrenergic receptor and inhibitors of the associated signaling pathway, whereas inhibition of β2-adrenergic cascade has no effect. In astrocytes in primary cultures, stimulation of β1-adrenergic receptor increases the activity of both Na,K-ATPase and Na–K–Cl cotransporter NKCC1. Here we discuss mechanisms underlying the effects of β1-adrenergic receptor activation on brain edema, with particular emphasis on the signaling pathway of β1-adrenergic receptor, extracellular ions and mitogen-activated protein kinase/ERK1/2 cascade during ischemia and reperfusion periods.