Sakurai E, Gunji E, Iizuka Y, Hikichi N, Maeyama K, Watanabe T
Department of Pharmaceutics, Tohoku College of Pharmacy, Sendai, Japan.
J Pharmacol Toxicol Methods. 1993 Apr;29(2):105-9. doi: 10.1016/1056-8719(93)90058-m.
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.
一种结合了高灵敏度高效液相色谱法的体内微透析方法已被用于测定血液中的组胺浓度，该高效液相色谱法是为分析中枢神经系统中的介质而开发的。这项技术被用于研究化合物48/80和组胺受体拮抗剂对大鼠血液中组胺释放的影响。通过体内微透析测量的血液中组胺的平均基础水平为177.8±11.1 pmol/mL。腹腔注射生理盐水对该水平没有显著影响，注射生理盐水后至少8小时该水平保持恒定。腹腔注射组胺（0.5 mg/kg）后，在颈静脉血液中很快检测到组胺。此外，由于透析液中回收的组胺与血液中的游离部分成正比，血液的体内微透析方法是检测组胺释放到血液中的可靠方法。在我们的实验中，化合物48/80（2.0 mg/kg，腹腔注射）使大鼠颈静脉透析液中的组胺水平显著升高，表明组胺从肥大细胞释放到血液中。然而，腹腔注射组胺受体拮抗剂，如吡苄明（2.0 mg/kg）、右氯苯那敏（2.0 mg/kg）、西咪替丁（10 mg/kg）或硫丙酰胺（10 mg/kg）后，组胺浓度没有升高。因此，目前的结果表明这些组胺受体拮抗剂可能对组胺释放到血液中没有影响。
