気管支喘息におけるムスカリン性アセチルコリン受容体に関する臨床的および実験的検討

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  • Clinical and experimental investigation on muscarinic acetylcholine receptor in bronchial asthma

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Clinical and experimental studies of bronchial hyperreactivity of asthma were performed with respect to muscarinic acetylcholine receptors (mACh-R). The characteristics of mACh-R in the guinea pig pulmonary tissues and in human lymphocytes were assessed by determining the affinity and density using ^3H-quinuclidinyl benzilate, a potent muscarinic antagonist. Furthermore, the characteristics of guinea pig M1-receptors were evaluated using ^3H-pirenzepine, a selective muscarinic antagonist. Ovalbumine-sensitized guinea pigs and control animals were used, and the influence of some drugs and neuropeptides on mACh-R was also investigated. There was a correlation between mACh-R (Bmax) of human peripheral lymphocytes and bronchial hypersensitivity (Dmin. in asthograph). The density of mACh-R in OA-sensitized guinea pigs (165.3±51.8 fmol/mg prot.) was three times as high as that in the control group (55.1±4.8fmol/mg prot.), and there was no difference between the affinity of the OA-sensitized group and control group The measurement of M1-receptors, revealed that this increase of mACh-R was due to the increase of M2 and other receptors. mACh-R (Bmax) decreased by administration of the beta agonist and muscarinic agonist, but the affinity (Kd) of mACh-R did not change. The density of mACh-R was not changed by administration with glucocorticoids, but Saibokutou (TJ-96) decreased markedly the density of mACh-R. The neuropeptide, Substance P decreased the density of mACh-R whereas the vasoactive intestinal peptide increased it.

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