Hegemann L, van Rooijen L A, Traber J, Schmidt B H
Department of Neurobiology, Troponwerke GmbH & Co. KG, Cologne, F.R.G.
Eur J Pharmacol. 1991 May 25;207(1):17-22. doi: 10.1016/s0922-4106(05)80032-x.
Polymyxin B, a cyclic peptide antibiotic, is considered to be a rather selective antagonist of protein kinase C. This drug is therefore widely used to evaluate the involvement of protein kinase C in cellular processes. In the present study, we investigated the effects of polymyxin B on the activity of calmodulin-dependent cyclic 3':5'-nucleotide phosphodiesterase in vitro. The drug potently inhibited this enzyme (IC50 80 nM in the presence of 500 microM Ca2+), while about 200-fold higher concentrations were required to inhibit protein kinase C to the same extent. Phosphodiesterase inhibition was competitive with respect to Ca2+ and calmodulin. Evidence for the formation of a complex between polymyxin B and calmodulin was obtained by polyacrylamide gel electrophoresis under non-denaturing conditions, and by affinity chromatography of calmodulin on polymyxin B-agarose. We therefore suggest that, at least in vitro, polymyxin B is a potent and selective inhibitor of calmodulin.
多粘菌素B是一种环肽抗生素，被认为是蛋白激酶C的一种相当有选择性的拮抗剂。因此，这种药物被广泛用于评估蛋白激酶C在细胞过程中的参与情况。在本研究中，我们在体外研究了多粘菌素B对钙调蛋白依赖性环3',5'-核苷酸磷酸二酯酶活性的影响。该药物能有效抑制这种酶（在500微摩尔/升钙离子存在下，半数抑制浓度为80纳摩尔），而抑制蛋白激酶C达到相同程度则需要高约200倍的浓度。磷酸二酯酶抑制作用对钙离子和钙调蛋白具有竞争性。通过非变性条件下的聚丙烯酰胺凝胶电泳以及钙调蛋白在多粘菌素B -琼脂糖上的亲和层析，获得了多粘菌素B与钙调蛋白之间形成复合物的证据。因此，我们认为，至少在体外，多粘菌素B是钙调蛋白的一种有效且有选择性的抑制剂。
