Changes in brain microvessel endothelial cell monolayer permeability induced by adrenergic drugs

Abstract

Brain microvessel endothelial cell monolayers have been shown to be a suitable blood-brain barrier in vitro system to study adrenergic regulation of permeability. We tested adrenergic drugs on bovine brain microvessel endothelial cell monolayer permeability to a biomembrane impermeant molecule, sodium fluorescein. Endonenous catecholamines noradrenaline and adrenaline were tested as well as the α-adrenoceptor agonist phenylephrine, the β-adrenoceptor agonist clenbuterol and the α-adrenoceptor antagonist prazosin. Results showed an α-adrenoceptor mediated increase and a β-adrenoceptor mediated decrease in monolayer permeability. Both α- and β-adrenoceptor mediated changes in permeability were abolished by inhibiting fluid-phase pinocytosis, either by vincristine or by avoiding bovine brain microvessel endothelial cell's energy utilization. The reverse transport (i.e., from brain to blood side) was also influenced by adrenergic drugs; α- or β-adrenoceptor stimulation induced a permeability-reducing effect. We conclude that α-adrenoceptor stimulation increases bovine brain microvessel endothelial cell monolayer permeability and that β-adrenoceptor stimulation has the opposite effect. Reverse transport results obtained with β-adrenoceptor stimulation seem controversial and deserve further study. These results also support in vivo findings that demonstrated adrenergic influences on blood-brain barrier permeability.