Undem B J, Ellis J L, Meeker S, Fischer A, Canning B J
Johns Hopkins School of Medicine, Johns Hopkins Asthma and Allergy Center, Baltimore, Maryland, USA.
J Pharmacol Exp Ther. 1996 Aug;278(2):964-70.
Carbon monoxide, formed as a product of heme oxygenase activity, has been postulated to act as an intra- and intercellular messenger molecule. We addressed the hypothesis that heme oxygenase is involved in the relaxation of the guinea pig trachealis elicited by vasoactive intestinal peptide (VIP) or by electrical field stimulation. Immunohistochemical studies revealed the presence of heme oxygenase-II in airway smooth muscle and epithelium. Zinc protoporphyrin-IX (ZnPPn), an inhibitor of heme oxygenase, effectively inhibited VIP-induced relaxations of tracheal smooth muscle. Surprisingly, the potency of ZnPPn was increased if the drug was preincubated with the VIP solution before addition to the tissue bath. The relaxant responses to 3-morpholinosydnonimine were unaffected by ZnPPn. Zinc deuteroporphyrin-IX 2,4 bisglycol, a more potent inhibitor of heme oxygenase than ZnPPn, did not affect the VIP responses. ZnPPn (300 microM) had no effect on nonadrenergic, noncholinergic relaxations of the guinea pig trachea. These data indicate that although ZnPPn is an efficacous inhibitor of VIP-induced relaxations of the guinea pig trachealis, it is unlikely that heme oxygenase plays an important role in this response. Rather, the data are consistent with the hypothesis that ZnPPn inhibits the VIP response via an interaction with the VIP molecules themselves. Although the results demonstrate the existence of heme oxygenase-II in the guinea pig trachealis, they do not support the hypothesis that it plays a role in electrical field stimulation-induced nonadrenergic, noncholinergic relaxations.
一氧化碳作为血红素加氧酶活性的产物，被认为可作为细胞内和细胞间的信使分子。我们探讨了血红素加氧酶参与血管活性肠肽（VIP）或电场刺激引起的豚鼠气管舒张的假说。免疫组织化学研究显示气道平滑肌和上皮细胞中存在血红素加氧酶-II。血红素加氧酶抑制剂锌原卟啉-IX（ZnPPn）可有效抑制VIP诱导的气管平滑肌舒张。令人惊讶的是，如果在将药物添加到组织浴之前将其与VIP溶液预孵育，ZnPPn的效力会增强。对3-吗啉代亚磺酰亚胺的舒张反应不受ZnPPn影响。比ZnPPn更有效的血红素加氧酶抑制剂锌次卟啉-IX 2,4-双二醇对VIP反应没有影响。ZnPPn（300 microM）对豚鼠气管的非肾上腺素能、非胆碱能舒张没有影响。这些数据表明，虽然ZnPPn是VIP诱导的豚鼠气管舒张的有效抑制剂，但血红素加氧酶在这种反应中不太可能起重要作用。相反，数据与ZnPPn通过与VIP分子本身相互作用抑制VIP反应的假说一致。虽然结果证明豚鼠气管中存在血红素加氧酶-II，但它们不支持其在电场刺激诱导的非肾上腺素能、非胆碱能舒张中起作用的假说。
