NEW DEVELOPMENT OF PHARMACOLOGICAL RESEARCH FOR HISTAMINE : USING MAST CELL DEFICIENT RAT

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In this research project, using mast cell deficient (Ws/Ws) rats, roles of histamine in the pathophysiological conditions such as allergy, gastric ulcer and behavior have been investigated. There are at least two types of histamine pools : one is mast cell-histamine and another is nin-mast cell histamine. As mast cells contain high amount of histamine and are distributed widely, it was difficult to differentiate these two histamine pools. Ws/Ws rats, which has a mutation of c-kit receptor, completely deplete connective tissue type of mast cells. Therefore, histamine contents in tissues of Ws/Ws rats derive from non-mast cell histamine. We can clearly demonstrate the existence of non-mast cell histamine and its roles as follows.1.Histamine content in the brain of Ws/Ws rats is 63% of the congenic (+/+) rats and it decreased to 37% of the control level after treatment of alpha-fluoromethylhistidine, a suicide inhibitor of histidine decarboxylase. The remaining content of histamine might … More be due to other pool than mast cells and neuron. (J.Neurochem.65 : 791,1995)2.Using in vivo microdialysis technique, the relationship between edema formation and histamine release in the paw was studied. After treatment of compound 48/80, histamine release sharply occurs in 20 min and decreased gradually through 3 hrs in +/+ rats but no edema formation and histamine release was observed in Ws/Ws rats. Compound 48/80 stimulates histamine release from mast cells and edema formation. (Eur.J.Pharmacol.331 : 237,1997)3.In water immesion stress, plasma histamine levels increased biphasically in normal rats. In the first phase, it reached a peak at 15 min and the second increase was observed between 1.5-6 hrs. After gastrectomy, the second increasein plasma histamine disappeared. In Ws/Ws rats, the water immersion stress causes no first peak and aftr gastrectomy, both increases in plasma histamine disappeared. Non-immunological stimulant causes histamine release from mast cells after water immersion stress. Less