Serotonin Receptor Regulation of Eosinophil Transendothelial Migration

Abstract

Abstract The tryptophan amino acid metabolite, 5-hydroxytryptophan (5HTP), is a metabolic precursor of serotonin. 5HTP reduces allergic inflammation in the lung by inhibiting eosinophil migration across endothelial monolayers. Blocking the metabolic conversion of 5HTP to serotonin decreases inhibition of eosinophil migration, indicating that its metabolism is required for inhibition. Currently it is unknown if serotonin receptors are involved in mediating 5HTP function. We determined which serotonin receptors are expressed by endothelial cells and eosinophils by western blot and qPCR. There was expression of the serotonin receptors 1A, 1B, 3A, and 6. Function of the receptors in transendothelial migration was addressed. Selective receptor inhibitors for serotonin receptors 1A and 1B blocked 5HTP inhibition of migration. Current data suggests serotonin receptors are involved in 5HTP inhibition of transendothelial migration and thus may serve as a target for intervention during allergic inflammation. These results will help design ongoing clinical studies addressing whether 5HTP supplementation reduces allergic asthmatic responses.