Coexpression of ß1‐ and ß2‐Adrenergic Receptors on Bovine Brain Capillary Endothelial Cells in Culture

Abstract

The pharmacological study of the blood‐brain barrier has often been hampered by the unavailability of a large number of pure and fully differentiated brain capillary endothelial cells. Here we describe a homogeneous culture of brain capillary endothelial cells isolated from bovine brain (BBECs), which retain at least some phenotypic characteristics of the functional blood‐brain barrier: intercellular tight junctions and monoamine oxidase activity. These cells were subcultured in vitro, in the absence of any neuronal or glial influences, for > 100 doublings without any sign of senescence. The present study is focused on the expression of ß‐adrenergic receptors on BBECs. By Northern blot hybridization, subtype‐specific ligand binding, and cyclic AMP accumulation experiments, we demonstrate that ß₁‐ and ß₂‐adrenergic receptors are coexpressed (in the respective proportions of 42 and 58%) on BBEC membranes and are functionally coupled to adenylate cyclase. This is the first report documenting a significant number of ß₁‐adrenergic receptors on brain capillary endothelial cells. The results are discussed in light of the known noradrenergic innervation of brain capillaries.