THE REDUCTION IN VITRO IN VISCOSITY OF MUCOPROTEIN SOLUTIONS BY A NEW MUCOLYTIC AGENT, N‐ACETYL‐L‐CYSTEINE
THE REDUCTION IN VITRO IN VISCOSITY OF MUCOPROTEIN SOLUTIONS BY A NEW MUCOLYTIC AGENT, N‐ACETYL‐L‐CYSTEINE
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新型粘液溶解剂 N-乙酰-L-半胱氨酸在体外降低粘蛋白溶液的粘度
DOI：
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发表时间：
1963
影响因子：
5.2
通讯作者：
Sheffner
中科院分区：
文献类型：
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作者：
WACETYL;Sheffner
粘性粘液积聚是慢性支气管炎、肺气肿、肺结核和囊性纤维化等呼吸道慢性疾病中经常遇到的问题。众所周知，这些分泌物的高粘度主要是由于它们含有粘蛋白和脱氧核糖核酸。然而，在没有急性感染的情况下，分泌物可能基本上是粘液状的，已经从支气管分泌物中分离出粘蛋白，产量约为总氮的60%。在研制治疗肺部疾病的溶核剂的研究中，发现L半胱氨酸及其许多同系物能显著降低含有各种来源的粘蛋白的溶液的粘度。在这一发现之后，文献中出现了DL-青霉胺降低含有高浓度巨球蛋白的血清的粘度的报道，2以及小麦面筋的主要蛋白质麦谷蛋白溶液的特性粘度被二硫键断裂剂3显著降低。然而，在对核糖核酸酶4和人血清a L b~m n的研究中，用巯基化合物处理还原的蛋白质的特性粘度基本上与氧化形式的相同或高于其氧化形式。似乎很明显，用巯基或其他二硫键裂解剂处理蛋白质对特性粘度的影响可能会有所不同，这取决于蛋白质的天然构象和二硫键固定一级结构空间排列的程度。本研究旨在了解巯基化合物在降低粘蛋白溶液粘度中的作用模式和作用机理。此外，由于大多数实验都是使用从猪胃粘液中提取的部分纯化的粘蛋白制剂(MP-50)进行的，因此对这种物质进行了部分化学分析，并在此进行了报道。值得注意的是，N-乙酰-L-半胱氨酸(XAc)是本研究中使用最多的巯基化合物，因为它具有良好的粘液溶解活性、相对较轻的味道和气味、高度溶解的二硫化物氧化产物和较低的毒性而被选择用于临床研究。
The accumulation of viscid mucus is a problem frequently encountered in chronic diseases of the respiratory tract such as chronic bronchitis, emphysema, tuberculosis, and cystic fibrosis. I t is well known that the high viscosity of these secretions is due primarily to their content of mucoprotein and deoxyribonucleic acids. However, in the absence of acute infection, the secretions may be essentially mucoid, and mucoprotein has been isolated from bronchial secretions in yields of about 60 per cent of the total nitrogen.’ During the investigation to develop a niucolytic agent that would be useful in the treatment of pulmonary disease, i t was discovered that L-cysteine and many of its congeners markedly reduced the viscosity of solutions containing mucoproteins from various sources. Subsequent to this finding, reports appeared in the literature that DL-penicillamine reduced the viscosity of serum containing a high concentration of macroglobulins,2 and that the intrinsic viscosity of solutions of glutenin, the principal protein of wheat gluten, is reduced markedly by disulfide bond-cleaving agents3 However, in studies on ribonuclease4 and human serum a l b ~ m i n , ~ the intrinsic viscosity of protein reduced by treatment with sulfhydryl compounds was essentially the same as or higher than that of the oxidized form. I t seems evident that the effect on intrinsic viscosity resulting from the treatment of proteins with sulfhydryl or other disulfide bondcleaving agents may vary, depending on the native conformation of the protein and the degree to which disulfide bonds fix the spatial arrangement of the primary structure. The present study was conducted to obtain information concerning the mode and mechanism of action of sulfhydryl compounds in reducing the viscosity of mucoprotein solutions. In addition, since the majority of these experiments were performed with a partially purified mucoprotein preparation (MP-50) extracted from porcine gastric mucin, a partial chemical analysis of this material was obtained and is reported here. I t should he noted that N-acetyl-L-cysteine (XAC) was the sulfhydryl compound used most frequently in this investigation since it was chosen for clinical study on the basis of its good mucolytic activity, relatively slight taste and odor, highly soluble disulfide oxidation product and low order of toxicity.