Changes in brain microvessel endothelial cell monolayer permeability induced by adrenergic drugs.
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. Endogenous catecholamines noradrenaline and adrenaline were tested as well as the alpha-adrenoceptor agonist phenylephrine, the beta-adrenoceptor agonist clenbuterol and the alpha-adrenoceptor antagonist prazosin. Results showed an alpha-adrenoceptor mediated increase and a beta-adrenoceptor mediated decrease in monolayer permeability. Both alpha- and beta-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; alpha- or beta-adrenoceptor stimulation induced a permeability-reducing effect. We conclude that alpha-adrenoceptor stimulation increases bovine brain microvessel endothelial cell monolayer permeability and that beta-adrenoceptor stimulation has the opposite effect. Reverse transport results obtained with beta-adrenoceptor stimulation seem controversial and deserve further study. These results also support in vivo findings that demonstrated adrenergic influences on blood brain barrier permeability.
Department of Pharmaceutical Chemistry, University of Kansas, School of Pharmacy, Lawrence 66045-2504.
N
N
Borges
F
F
Shi
I
I
Azevedo
K L
KL
Audus
D018663:Adrenergic Agents / Q000494:pharmacology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects*; D002417:Cattle; D002976:Clenbuterol / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D010873:Pinocytosis / Q000187:drug effects; D011224:Prazosin / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
D018663:Adrenergic Agents; D010656:Phenylephrine; D014750:Vincristine; D009638:Norepinephrine; D011224:Prazosin; D002976:Clenbuterol; D004837:Epinephrine