A calcium-dependent reversible permeability increase in microvessels in frog brain, induced by serotonin

Abstract

The effect of serotonin on brain microvascular permeability was studied by measurement of changes in the electrical resistance of the venular vascular wall, induced by this substance. Intravenous administration of serotonin decreased the electrical resistance in a dose-dependent manner with Kd congruent to 8.2 microM. The maximal decrease in electrical resistance was about 33%. The electrical resistance fell within seconds following the application and returned to the control value after 1-5 min. Serotonin applied to the outside of the brain vessels had no effect on electrical resistance. Pre-treatment with the 5-HT2 receptor antagonist Ketanserin blocked the serotonin response completely. The serotonin response was strongly inhibited by pre-treatment with the calcium-entry blocker verapamil (Isoptin). The findings demonstrate that serotonin reversibly increases blood-brain barrier permeability. The effect is mediated via 5-HT2 receptors located at the luminal surface of the cerebrovascular endothelium and is dependent on mobilization of extracellular Ca2+.