纯化的红细胞钙泵ATP酶：在无钙调蛋白的情况下，推测的抗钙调蛋白药物直接抑制作用的证据。

Purified red blood cell Ca2+-pump ATPase: evidence for direct inhibition by presumed anti-calmodulin drugs in the absence of calmodulin.

作者信息

Vincenzi F F, Adunyah E S, Niggli V, Carafoli E

出版信息

Cell Calcium. 1982 Dec;3(6):545-59. doi: 10.1016/0143-4160(82)90044-6.

DOI:10.1016/0143-4160(82)90044-6

Abstract

A variety of presumed anti-calmodulin (anti-CaM) drugs was tested for their potential inhibitory effects on the isolated, purified and reconstituted Ca2+-pump ATPase of human red blood cell membranes. Anti-CaM drugs inhibited the Ca2+-pump ATPase both in the absence and presence of added CaM. Qualitatively similar inhibition was observed in two different ATPase assay systems. In asolectin vesicles in the absence of added CaM trifluoperazine (TFP), N-(6-aminohexyl)-5-chloro-1-naphthalene- sulfonamide (W-7), vinblastine, dibucaine, imipramine, propranolol and dimethylpropranolol (UM-272) were all inhibitory. Potency of anti-CaM drugs was generally greater on the enzyme reconstituted in asolectin vesicles than on the enzyme reconstituted in phosphatidylcholine vesicles, either in the presence or absence of CaM. The results emphasize that anti-CaM drugs have actions other than to bind to CaM. Possible direct interaction of amphipathic cationic anti-CaM drugs with the Ca2+-pump ATPase and/or its lipid environment is suggested.

摘要

测试了多种假定的抗钙调蛋白（抗CaM）药物对人红细胞膜分离、纯化和重组的Ca2+泵ATP酶的潜在抑制作用。抗CaM药物在添加CaM的情况下和未添加CaM的情况下均能抑制Ca2+泵ATP酶。在两种不同的ATP酶测定系统中观察到了定性相似的抑制作用。在未添加CaM的大豆卵磷脂囊泡中，三氟拉嗪（TFP）、N-（6-氨基己基）-5-氯-1-萘磺酰胺（W-7）、长春碱、丁卡因、丙咪嗪、普萘洛尔和二甲基普萘洛尔（UM-272）均具有抑制作用。无论是在存在还是不存在CaM的情况下，抗CaM药物对重组于大豆卵磷脂囊泡中的酶的效力通常比对重组于磷脂酰胆碱囊泡中的酶的效力更大。结果强调抗CaM药物除了与CaM结合外还有其他作用。提示两亲性阳离子抗CaM药物可能与Ca2+泵ATP酶和/或其脂质环境直接相互作用。