Regulation of signal transduction and GTP binding proteins for mucin release from submandibular glands

信号转导和 GTP 结合蛋白对下颌下腺粘蛋白释放的调节

• 批准号: 03670867
• 负责人: DOHI Toshihiro
• 金额: $ 1.34万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670867/
• 关键词: Submandibular gland; Mucin; Signal transduction; GTP binding protein; IP_3; Calcium; Cyclic ADP-ribose; Platelet-activating factor; イヌ顎下腺腺房細胞; 細胞内Ca^<2+>; Ca^<2+>動員; アセチルコリン; カルシウム; GTP結合蛋白質

It has been generally accepted that mucin release from submandibular gland is mediated by beta adrenergic receptor-adenylate cyclase system, and alpha adrenergic and muscarinic cholinergic systems are not involved in mucin release. However, we have previously shown that mucin release from dog submandibular gland is mainly mediated by muscarinic ACh receptor(mAChR)stimulation. The present study investigated signal transduction systems and GTP binding proteins coupled to mAChR for exocytosis in dog submandibular gland cells.Mucin release was stimulated by ACh, alpha adrenergic agonists, ionomycin and thapsigardin in Ca^<2+>-dependent manner. ACh increased intracellular free Ca^<2+> concentration ( [Ca^<2+>] i), IP_3 and IP_4. IP_3, ryanodine, cyclic ADP-ribose but not caffeine stimulated Ca^<2+> release in permeabilized cells. GTPgammaS in permeabilized cells and TPA increase mucin release. GTPgammaS stimlated DTT-insensitive choline-phosphotransferase activity for platelet-activating factor (PAF) synthesis. PAF inhibited membrane Na^+, K^+-ATPase activity and mobilized Ca^<2+> in permeabilized cells.These results suggest that mAChR stimulation causes mucin release by increasing [Ca^<2+>] i through IP_3-mediated mobilization of Ca^<2+> from intracellular stores, stimulation of Ca^<2+> induced Ca^<2+> release mechanism and activation of Ca^<2+> entry mechanism through plasma membrane. PKC and GTP binding proteins may be involved in mucin release and PAF synthesis, and serve as signal transduction systems in dog submandibular glands.

一般认为，下颌下腺粘蛋白的释放是由β肾上腺素能受体-腺苷酸环化酶系统介导的，而α肾上腺素能和毒蕈碱胆碱能系统不参与粘蛋白的释放。然而，我们以前已经表明，粘蛋白从狗颌下腺释放主要是介导的毒蕈碱乙酰胆碱受体（mAChR）的刺激。本实验研究了乙酰胆碱（ACh）、α-肾上腺素能受体激动剂、离子霉素和毒胡萝卜素（thapsigardin）对狗下颌下腺细胞分泌粘蛋白的影响。ACh增加细胞内游离Ca^<2+>浓度（[Ca^<2+] i）、IP_3和IP_4。IP_3、ryanodine、环ADP核糖而非咖啡因刺激透化细胞的Ca^2+释放。透化细胞中的GTP γ S和TPA增加粘蛋白释放。GTP γ S刺激血小板活化因子（PAF）合成的DTT不敏感胆碱磷酸转移酶活性。PAF抑制透性化细胞膜Na^+，K^+-ATP酶活性和Ca^2+动员，提示mAChR刺激通过IP_3介导的胞内Ca^2+动员、激活Ca^2+诱导的Ca ^2+释放机制和激活Ca^2+经质膜进入机制，增加[Ca^2 +] i，从而引起粘蛋白释放。PKC和GTP结合蛋白可能参与狗颌下腺粘蛋白的释放和PAF的合成，并作为信号转导系统。

项目成果

H.Yamaki: "Mucin release from submandibular gland cells induced by calcium ion" The Journal of Hiroshima University Dental Society. 26 (1). 14-28 (1994)

H.Yamaki：“钙离子诱导下颌下腺细胞粘蛋白释放”广岛大学牙科学会杂志。

山木 博司: "イヌ顎下腺細胞からのカルシウムイオン動員によるムチン分泌" 広島大学歯学雑誌. 26. 14-28 (1994)

Hiroshi Yamaki：“犬颌下腺细胞钙离子动员的粘蛋白分泌”广岛大学牙科杂志 26. 14-28 (1994)。

H.Ohtsuki: "Involvement of Ca^<2+> entry and inositol trisphosphateーinduced internal Ca^<2+> mobilization in muscarinic receptorーmediated catecholamine release in dog adrenal Chromaffin cells." Neurochemistry International.

H. Ohtsuki：“狗肾上腺嗜铬细胞中毒蕈碱受体介导的儿茶酚胺释放中 Ca ^ 2+ 进入和肌醇三磷酸诱导的内部 Ca ^ 2+ 动员的参与。”

H.Ohtsuki,K.Morita,N.Minami,T.Suemitsu,A.Tsujimoto and T.Dohi: "Involvement of Ca^<2+> entry and inositol trisphosphate-induced internal Ca^<2+> mobilization in muscarinic receptor-mediated catecholamine release in dog adrenal chromaffin cells." Neurochem

H.Ohtsuki、K.Morita、N.Minami、T.Suemitsu、A.Tsujimoto 和 T.Dohi：“毒蕈碱受体介导中 Ca^2 进入和肌醇三磷酸诱导的内部 Ca^2 动员的参与

H.Ohtsuki, K.Morita, N.Minami, T.Suemitsu, A.Tsujimoto and T.Dohi: "Involvement of Ca^<2+> entry and inositol trisphosphate-induced internal Ca^<2+> mobilization in muscarinic receptor-mediated catecholamine release in dog adrenal chromaffin cells" Neuroc

H.Ohtsuki、K.Morita、N.Minami、T.Suemitsu、A.Tsujimoto 和 T.Dohi：“毒蕈碱受体介导中 Ca^2 进入和肌醇三磷酸诱导的内部 Ca^2 动员的参与