Calmodulin and Cyclic AMP: Possible Different Sites of Action of These Two Regulatory Agents in Exocytotic Hormone Release
Calmodulin and Cyclic AMP: Possible Different Sites of Action of These Two Regulatory Agents in Exocytotic Hormone Release
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钙调蛋白和环 AMP：这两种调节剂在胞吐激素释放中可能的不同作用位点
DOI：
10.2337/diab.33.4.339
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发表时间：
1984
期刊：
影响因子：
7.7
通讯作者：
K. Sussman
中科院分区：
文献类型：
--
作者：
J. P. Steinberg;J. Leitner;B. Draznin;K. Sussman
现在有可能确定某些细胞内事件，这些事件专门影响分泌-颗粒融合到质膜或颗粒溶解。分离的大鼠胰岛中的分泌囊似乎将生长抑素(SRIF)受体从高尔基体转移到质膜上。我们提出，分泌颗粒与质膜的融合可以通过测量SRIF受体对质膜的募集来确定。颗粒溶解可通过测量胰岛素释放来评估。为了激活cAMP(CAMP)依赖的通路，我们使用了异丁基甲基黄嘌呤(IBMX，400μM)、胰高血糖素(10μM)和腺苷环化酶二萜激活剂Forsklin(20μM)。这些药物均能引起胰岛素的快速释放(分别为0.41±0.02~1.88±0.02；0.41±0.02~1.93±0.08；0.41±0.02~1.66±0.03μU/μ/min，P<；0.001)。没有伴随的SRIF受体的募集。生长抑素(10μg/ml)抑制cAMP刺激的蛋白磷酸化，抑制IBMX、胰高血糖素或Forsklin诱导的胰岛素释放(抑制率分别为80%、75%或82%)。相反，钙调素抑制剂三氟拉嗪(10μM)并不抑制通过cAMP依赖途径诱导的胰岛素释放。三氟拉嗪抑制葡萄糖诱导的胰岛素释放和SRIF受体在细胞膜上的募集，提示钙调蛋白可能在促进分泌-颗粒与质膜融合中起作用。这些数据表明，颗粒与质膜的融合可能是钙调蛋白的一种功能。相反，cAMP在多肽激素分泌中的主要作用部位可能是促进分泌颗粒的溶解和相关激素的释放。
It may now be possible to identify certain intracellular events that impact specifically on secretion-granule fusion to the plasma membrane or on granule lysis. Secretion vesicles in isolated rat islets appear to translocate somatostatin (SRIF) receptors from the Golgi apparatus to the plasma membrane. We have proposed that secretion granule fusion to the plasma membrane can be determined by measuring recruitment of SRIF receptors to the surface membrane. Granule lysis can be assessed by measuring insulin release. To activate cyclic AMP (cAMP)-dependent pathways, we employed isobutylmethylxanthine (IBMX, 400 μM), glucagon (10 μM), and forskolin (20 μM), a diterpene activator of adenylate cyclase. These agents evoked rapid release of insulin (from 0.41 ± 0.02 to 1.88 ± 0.02; 0.41 ± 0.02 to 1.93 ± 0.08; and 0.41 ± 0.02 to 1.66 ± 0.03 μU/islet/ min, respectively, P < 0.001). There was no concomitant recruitment of SRIF receptors. Somatostatin (10 μg/ml), which inhibits cAMP-stimulated protein phosphorylation, suppresses insulin release evoked by IBMX, glucagon, or forskolin (inhibition: 80, 75, or 82%, respectively). In contrast, trifluoperazine (10 μM), an inhibitor of calmodulin, did not suppress insulin release induced through cAMP-dependent pathways. Trifluoperazine suppresses glucose-induced insulin release and the recruitment of SRIF receptors to the surface membrane, suggesting the possible role of calmodulin in promoting secretion-granule fusion with the plasma membrane. These data suggest that granule fusion to the plasma membrane may be a calmodulin-directed function. In contrast, the major site of action of CAMP in polypeptide hormone secretion may be in promoting lysis of secretion granules and associated hormone discharge.
完整仓鼠胰岛素瘤细胞中 Ca2 依赖性蛋白磷酸化和胰岛素释放。
DOI：
--
发表时间：
1980
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Schubart,UK;Fleischer,N;Erlichman,J
通讯作者：
Erlichman,J
DOI：
10.1016/s0021-9258(18)33705-0
发表时间：
1982-10
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
U. Schubart
通讯作者：
U. Schubart
胰岛素释放和蛋白质磷酸化：钙调蛋白的可能作用。
DOI：
--
发表时间：
1982
期刊：
Federation proceedings
影响因子：
--
作者：
Schubart,UK;Erlichman,J;Fleischer,N
通讯作者：
Fleischer,N