Sobel D O, Shakir K M
Georgetown University, Department of Pediatrics, Washington, DC 20007.
Peptides. 1988 Sep-Oct;9(5):1037-42. doi: 10.1016/0196-9781(88)90085-x.
Monensin is a sodium selective carboxylic ionophore that has been helpful in studying the intracellular mechanisms of protein secretion by its ability to inhibit transport of secretory proteins, particularly through the Golgi apparatus, and by its capacity to block intracellular posttranslational processing events. We studied in rat anterior pituitary cell culture the effects of monensin on: CRF stimulated ACTH release; presynthesized (stored) ACTH release; and on forskolin- (activator of adenylate cyclase) and KCl- (a membrane depolarizer which does not stimulate ACTH synthesis) induced ACTH release. Monensin inhibited CRF stimulated ACTH release in a dose-dependent fashion. The ED50 was 2.7 x 10(-8) M and maximal inhibition was 52% at 1.5 x 10(-7) M. Inhibition at 40 minutes of CRF incubation was similar to the percent inhibition noted at 1 hr 40 min and 2 hr 40 min. Monensin (1.5 x 10(-6) M) decreased the amount of ACTH release from cells incubated with cycloheximide plus CRF by 32% (p less than 0.01). Monensin individually inhibited forskolin (2 x 10(-6) M) and dibutyryl cyclic AMP (3 x 10(-3) M) mediated ACTH release in a dose-dependent fashion. The inhibition of forskolin and dibutyryl cyclic AMP mediated ACTH release by 1.5 x 10(-6) M monensin was 48% and 46% respectively. Monensin (1.5 x 10(-6) M) also reduced KCl (50 mM) stimulated ACTH release by 48%. This study demonstrates that monensin inhibits CRF mediated ACTH release.(ABSTRACT TRUNCATED AT 250 WORDS)
莫能菌素是一种钠选择性羧酸离子载体，它通过抑制分泌蛋白的转运，特别是通过高尔基体的转运，以及通过阻断细胞内翻译后加工事件的能力，有助于研究蛋白质分泌的细胞内机制。我们在大鼠垂体前叶细胞培养中研究了莫能菌素对以下方面的影响：促肾上腺皮质激素释放因子（CRF）刺激的促肾上腺皮质激素（ACTH）释放；预合成（储存）的ACTH释放；以及对福斯可林（腺苷酸环化酶激活剂）和氯化钾（一种不刺激ACTH合成的膜去极化剂）诱导的ACTH释放的影响。莫能菌素以剂量依赖的方式抑制CRF刺激的ACTH释放。半数有效剂量（ED50）为2.7×10⁻⁸M，在1.5×10⁻⁷M时最大抑制率为52%。CRF孵育40分钟时的抑制率与1小时40分钟和2小时40分钟时的抑制率百分比相似。莫能菌素（1.5×10⁻⁶M）使与放线菌酮加CRF一起孵育的细胞释放的ACTH量减少了32%（p<0.01）。莫能菌素单独以剂量依赖的方式抑制福斯可林（2×10⁻⁶M）和二丁酰环磷腺苷（3×10⁻³M）介导的ACTH释放。1.5×10⁻⁶M莫能菌素对福斯可林和二丁酰环磷腺苷介导的ACTH释放的抑制率分别为48%和46%。莫能菌素（1.5×10⁻⁶M）也使氯化钾（50mM）刺激的ACTH释放减少了48%。这项研究表明莫能菌素抑制CRF介导的ACTH释放。（摘要截短至250字）
