IN-VIVO MICRODIALYSIS MEASUREMENT OF 5-HYDROXYTRYPTAMINE AND ITS METABOLITES, 5-HYDROXYINDOLEACETIC ACID AND N-ACETYL 5-HYDROXYTRYPTAMINE, IN RAT-BLOOD - EFFECTS OF HISTAMINE-RECEPTOR ANTAGONISTS

The blood concentrations of 5-hydroxytryptamine (5-HT) and its metabol ites, 5-hydroxyindoleacetic acid (5-HIAA) and N-acetyl 5-HT were assay ed by in-vivo microdialysis and a highly sensitive HPLC procedure that was originally developed to analyse CNS mediators. We investigated th e effects of histamine-receptor antagonists on 5-HT metabolism and its release into the blood of rats. The mean basal levels of 5-HT, 5-HIAA and N-acetyl 5-HT in the blood measured by in-vivo microdialysis were 77.2 +/- 9.4, 20.3 +/- 1.5 and 1.89 +/- 0.15 pmol mL(-1) respectively . These levels were not significantly affected by an intraperitoneal i njection of saline, and remained at constant levels for at least 8 h a fter administration of saline. After an intraperitoneal injection of 5 -HT hydrochloride (0.5 mg kg(-1)), 5-HT was soon detected in the blood of the jugular vein. 5-HIAA also quickly appeared in the blood and de clined monoexponentially from 60 min after injection. In contrast, N-a cetyl 5-HT slowly appeared in the blood and it reached a maximal level at 270 min. The 5-HT and N-acetyl 5-HT levels in dialysates from rat jugular vein were significantly increased by intraperitoneal pyrilamin e (2.0 mg kg(-1)), (+)-chlorpheniramine (2.0 mg kg(-1)) and cimetidine (20.0 mg kg(-1)). However, there was no increase in the 5-HIAA concen tration after an intraperitoneal injection of these histamine-receptor antagonists, demonstrating that the 5-HT released from various cells containing 5-HT was predominantly metabolized to N-acetyl 5-HT by N-ac etyltransferase. Moreover, thioperamide did not affect the basal level s of 5-HT, 5-HIAA or N-acetyl 5-HT. Because the recovered 5-HT, 5-HIAA and N-acetyl 5-HT in the dialysate is directly proportional to the fr ee fraction in the blood, in-vivo microdialysis is a reliable method o f examining 5-HT metabolism and its release into the blood.