Nagai H, Yamada H, Goto S, Inagaki N, Koda A
Int Arch Allergy Appl Immunol. 1985;76(3):251-5. doi: 10.1159/000233700.
The effect of two calmodulin inhibitors, 1-[bis(p-chlorophenyl)methyl]-3-[2,4-dichloro-beta-(2,4-dichlorobenzylox y) phenethyl]imidazolinium chloride (R 24571) and chlorpromazine (CPZ) on antigen-induced contraction of guinea-pig tracheal smooth muscle was studied. Ketotifen, an anti-allergic compound, was used as a comparative drug. Contraction of sensitized guinea-pig trachea induced by antigen challenge was reduced by all three agents. The two calmodulin inhibitors effected relaxation of contraction of guinea-pig trachea induced by histamine and leukotriene D4 (LTD4). Ketotifen relaxed histamine-induced contraction, but hardly affected LTD4-induced tone. Contrary to chemical mediator induced tone, all examined agents had no effect on resting tone. These three agents shifted histamine- and LTD4-induced concentration-contraction curves to the right. They produced a downward displacement of the maximum, without a parallel shift in histamine- and LTD4-induced concentration-contraction curves. The two calmodulin inhibitors did not affect the antigen-induced release of histamine and SRS-A from sensitized guinea-pig lung tissue. Ketotifen slightly inhibited the release of histamine. These results suggest that R 24571 and CPZ, calmodulin inhibitors, reduced an antigen-induced contraction of sensitized guinea-pig trachea in vitro mainly by affecting the contractility of tracheal smooth muscle by chemical mediators but not by interfering with the release of mediators.
研究了两种钙调蛋白抑制剂，1-[双（对氯苯基）甲基]-3-[2,4-二氯-β-（2,4-二氯苄氧基）苯乙基]咪唑啉氯化物（R 24571）和氯丙嗪（CPZ）对豚鼠气管平滑肌抗原诱导收缩的影响。抗组胺化合物酮替芬用作对照药物。三种药物均能减轻抗原攻击引起的致敏豚鼠气管收缩。两种钙调蛋白抑制剂可使组胺和白三烯D4（LTD4）诱导的豚鼠气管收缩舒张。酮替芬可舒张组胺诱导的收缩，但对LTD4诱导的张力几乎没有影响。与化学介质诱导的张力相反，所有检测药物对静息张力均无影响。这三种药物使组胺和LTD4诱导的浓度-收缩曲线右移。它们使最大值向下移位，而组胺和LTD4诱导的浓度-收缩曲线没有平行移位。两种钙调蛋白抑制剂不影响致敏豚鼠肺组织中抗原诱导的组胺和慢反应物质A（SRS-A）释放。酮替芬轻微抑制组胺释放。这些结果表明，钙调蛋白抑制剂R 24571和CPZ在体外减轻致敏豚鼠气管抗原诱导的收缩，主要是通过影响化学介质对气管平滑肌的收缩性，而不是通过干扰介质的释放。
