Safayhi H, Kühn M, Koopmann I, Ammon H P
Department of Pharmacology, University of Tübingen, Federal Republic of Germany.
Naunyn Schmiedebergs Arch Pharmacol. 1989 Jan-Feb;339(1-2):8-13. doi: 10.1007/BF00165119.
CGS 9343B:1,3-Dihydro-1-[1-[4-methyl-4H,6H-pyrrolo[1,2-a]-[4,1] benzoxazepin-4-yl)methyl)-4-piperidinyl]-2H-benzimidazol-2-o ne maleate and W7:N-6(aminohexyl)-5-chloro-1-naphthalenesulfonamide) are calmodulin antagonists with different specificities. The effects of CGS 9343B and W7 on cytosolic free calcium concentration ([ Ca2+]i) and insulin release were investigated in rat insulinoma cells (RINm5F). As measured with the Quin-2 technique, preincubation with CGS 9343B (0.3-10 microM) and W7 (5-50 microM) concentration dependently decreased KCl (25 mM)-mediated accumulation of cytosolic calcium. Both, CGS 9343B (10 microM) and W7 (50-100 microM) almost abolished the alanine- and KCl-induced increase in [Ca2+]i and significantly inhibited KCl (25 mM)- and alanine (10 mM)-mediated insulin release. W5 (100 microM), the chlorine-deficient analogue of W7 with decreased affinity for calmodulin, did not inhibit the KCl-induced increase in [Ca2+]i and enhanced basal and KCl-mediated insulin release by 56% and 189%, respectively. Our data suggest that CGS 9343B and W7 inhibit the depolarization-induced calcium uptake and subsequent increase in [Ca2+]i.
CGS 9343B：1,3 - 二氢 - 1 - [1 - [4 - 甲基 - 4H,6H - 吡咯并[1,2 - a] - [4,1]苯并二氮杂卓 - 4 - 基）甲基] - 4 - 哌啶基] - 2H - 苯并咪唑 - 2 - 酮马来酸盐和W7：N - 6（氨基己基） - 5 - 氯 - 1 - 萘磺酰胺是具有不同特异性的钙调蛋白拮抗剂。在大鼠胰岛素瘤细胞（RINm5F）中研究了CGS 9343B和W7对细胞质游离钙浓度（[Ca2 +]i）和胰岛素释放的影响。用Quin - 2技术测量，用CGS 9343B（0.3 - 10 microM）和W7（5 - 50 microM）预孵育浓度依赖性地降低了KCl（25 mM）介导的细胞质钙积累。CGS 9343B（10 microM）和W7（50 - 100 microM）均几乎消除了丙氨酸和KCl诱导的[Ca2 +]i增加，并显著抑制了KCl（25 mM）和丙氨酸（10 mM）介导的胰岛素释放。W5（100 microM）是W7的氯缺乏类似物，对钙调蛋白的亲和力降低，不抑制KCl诱导的[Ca2 +]i增加，分别使基础胰岛素释放和KCl介导的胰岛素释放增强了56％和189％。我们的数据表明，CGS 9343B和W7抑制去极化诱导的钙摄取以及随后[Ca2 +]i的增加。
