Abstract
The effect of serotonin [5-hydroxytryptamine, 5-HT] on brain microvascular permeability was studied by measurement of changes in the electrical resistance of the venular vascular wall, induced by this substance. I.v. administration of 5-HT decreased the electrical resistance in a dose-dependent manner with Kd .simeq. 8.2 .mu.M. The maximal decrease in electrical resistance was .apprx. 33%. The electrical resistance fell within seconds following the application and returned to the control value after 1-5 min. 5-HT 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 5-HT response completely. The 5-HT response was strongly inhibited by pre-treatment with the C.sbd.entry blocker verapamil (Isoptin). 5-HT 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+.