INVIVO MICRODIALYSIS MEASUREMENT OF HISTAMINE IN RAT-BLOOD EFFECTS OFCOMPOUND-48 80 AND HISTAMINE-RECEPTOR ANTAGONISTS/

An in vivo microdialysis method combined with a highly sensitive HPLC method which was developed for the analysis of the mediators in the CN S has been applied to assay histamine concentrations in the blood. The technique was used to study the effects of compound 48/80 and histami ne receptor antagonists on histamine release in the blood of rats. The mean basal level of histamine in the blood measured by in vivo microd ialysis was 177.8 +/- 11.1 pmol/mL. This level was not affected signif icantly by intraperitoneal (i.p.) injection of saline, and remained at the constant level for at least 8 hr after injection of saline. After i.p. injection of histamine (0.5 mg/kg), histamine was quickly detect ed in the blood of the jugular vein. Moreover, because the recovered h istamine in the dialysate is directly proportional to the free fractio n in the blood, the in vivo microdialysis method of blood is a reliabl e method of examining histamine release into the blood. In our experim ents, the histamine level in dialysates from rat jugular vein was mark edly increased by compound 48/80 (2.0 mg/kg, i.p.), demonstrating the histamine release into the blood from mast cells. However, there was n o increase in histamine concentration after an i.p. injection of hista mine receptor antagonists, such as pyrilamine (2.0 mg/kg), d-chlorphen iramine (2.0 mg/kg), cimetidine (10 mg/kg), or thioperamide (10 mg/kg) . Thus, the present results suggested that these histamine receptor an tagonists might not have an influence on histamine release into the bl ood.