An in vivo microdialysis method combined with a highly sensitive HPLC method which was developed for the analysis of the mediators in the CNS has been applied to assay histamine concentrations in the blood. The technique was used to study the effects of compound 48/80 and histamine receptor antagonists on histamine release in the blood of rats. The mean basal level of histamine in the blood measured by in vivo microdialysis was 177.8 +/- 11.1 pmol/mL. This level was not affected significantly 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 detected in the blood of the jugular vein. Moreover, because the recovered histamine in the dialysate is directly proportional to the free fraction in the blood, the in vivo microdialysis method of blood is a reliable method of examining histamine release into the blood. In our experiments, the histamine level in dialysates from rat jugular vein was markedly increased by compound 48/80 (2.0 mg/kg, i.p.), demonstrating the histamine release into the blood from mast cells. However, there was no increase in histamine concentration after an i.p. injection of histamine receptor antagonists, such as pyrilamine (2.0 mg/kg), d-chlorpheniramine (2.0 mg/kg), cimetidine (10 mg/kg), or thioperamide (10 mg/kg). Thus, the present results suggested that these histamine receptor antagonists might not have an influence on histamine release into the blood.
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