氟化物而非佛博尔酯刺激大鼠膀胱前列腺素合成:G蛋白和蛋白激酶C作用的研究

J.Y. Jeremy, P. Dandona
{"title":"氟化物而非佛博尔酯刺激大鼠膀胱前列腺素合成:G蛋白和蛋白激酶C作用的研究","authors":"J.Y. Jeremy,&nbsp;P. Dandona","doi":"10.1016/0262-1746(87)90002-3","DOIUrl":null,"url":null,"abstract":"<div><p>The role of G proteins and protein kinase C in mediating muscarine receptor-linked prostanoid synthesis by the rat urinary bladder was investigated using the G protein activator, sodium fluoride (NaF); the protein kinase C activators, phorbol myristate (PMA) and phorbol dibutyrate (PDBU); the protein kinase C inhibitor, H7, and the parasympathomimetic, carbachol. NaF stimulated in vitro rat urinary bladder prostacyclin (PGI<sub>2</sub>) synthesis (EC<sub>50</sub> = 6 mmol. <sup>−1</sup>), an action inhibited by the presence of EDTA (10 mmol. 1<sup>−1</sup>). Carbachol potentiated the stimulatory action of NaF. NaF (10 mmol.l<sup>−1</sup>)-stimulated PGI<sub>2</sub> synthesis was inhibited by the calcium channel blockers verapamil, nifedipine and the protein kinase C inhibitor, H7, in concentrationdependent manners. Carbachol-stimulated PGI<sub>2</sub> synthesis was also inhibited by H7. PDBU and PMA were without effect on de novo, NaF-or carbachol-stimulated urinary bladder PGI<sub>2</sub> synthesis. Other prostanoids (PGE<sub>2</sub> and PGF<sub>2α</sub>) were stimulated to the same degree as PGI<sub>2</sub> by NaF, and inhibited equally by H7 and calcium channel blockers. Dibutyryl adenosine 3′:5′-cyclic monophosphate was without effect on de novo or NaF-stimulated prostanoid synthesis. Since fluoride activates G proteins, these data indicate that: (1) muscarine receptorprostanoid synthesis coupling is mediated by G proteins in the rat urinary bladder; (2) fluoride action is mediated by protein kinase C and not adenyl cyclase, probably through activation of phospholipase C and therefore the generation of the protein kinase C activator diacyl glycerol; (3) activated protein kinase C may initiate Ca<sup>2++</sup> mobilisation linked to prostanoid synthesis; and (4) the lack of effect of the phorbol esters on urinary bladder PGI<sub>2</sub> synthesis, in contrast to that on other smooth muscle, indicates that in different smooth muscle tissues there are varying forms of protein kinase C.</p></div>","PeriodicalId":20720,"journal":{"name":"Prostaglandins, leukotrienes, and medicine","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"1987-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0262-1746(87)90002-3","citationCount":"6","resultStr":"{\"title\":\"Fluoride but not phorbol esters stimulate rat urinary bladder prostanoid synthesis: Investigations into the roles of G proteins and protein kinase C\",\"authors\":\"J.Y. Jeremy,&nbsp;P. Dandona\",\"doi\":\"10.1016/0262-1746(87)90002-3\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>The role of G proteins and protein kinase C in mediating muscarine receptor-linked prostanoid synthesis by the rat urinary bladder was investigated using the G protein activator, sodium fluoride (NaF); the protein kinase C activators, phorbol myristate (PMA) and phorbol dibutyrate (PDBU); the protein kinase C inhibitor, H7, and the parasympathomimetic, carbachol. NaF stimulated in vitro rat urinary bladder prostacyclin (PGI<sub>2</sub>) synthesis (EC<sub>50</sub> = 6 mmol. <sup>−1</sup>), an action inhibited by the presence of EDTA (10 mmol. 1<sup>−1</sup>). Carbachol potentiated the stimulatory action of NaF. NaF (10 mmol.l<sup>−1</sup>)-stimulated PGI<sub>2</sub> synthesis was inhibited by the calcium channel blockers verapamil, nifedipine and the protein kinase C inhibitor, H7, in concentrationdependent manners. Carbachol-stimulated PGI<sub>2</sub> synthesis was also inhibited by H7. PDBU and PMA were without effect on de novo, NaF-or carbachol-stimulated urinary bladder PGI<sub>2</sub> synthesis. Other prostanoids (PGE<sub>2</sub> and PGF<sub>2α</sub>) were stimulated to the same degree as PGI<sub>2</sub> by NaF, and inhibited equally by H7 and calcium channel blockers. Dibutyryl adenosine 3′:5′-cyclic monophosphate was without effect on de novo or NaF-stimulated prostanoid synthesis. Since fluoride activates G proteins, these data indicate that: (1) muscarine receptorprostanoid synthesis coupling is mediated by G proteins in the rat urinary bladder; (2) fluoride action is mediated by protein kinase C and not adenyl cyclase, probably through activation of phospholipase C and therefore the generation of the protein kinase C activator diacyl glycerol; (3) activated protein kinase C may initiate Ca<sup>2++</sup> mobilisation linked to prostanoid synthesis; and (4) the lack of effect of the phorbol esters on urinary bladder PGI<sub>2</sub> synthesis, in contrast to that on other smooth muscle, indicates that in different smooth muscle tissues there are varying forms of protein kinase C.</p></div>\",\"PeriodicalId\":20720,\"journal\":{\"name\":\"Prostaglandins, leukotrienes, and medicine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":0.0000,\"publicationDate\":\"1987-10-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://sci-hub-pdf.com/10.1016/0262-1746(87)90002-3\",\"citationCount\":\"6\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Prostaglandins, leukotrienes, and medicine\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/0262174687900023\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Prostaglandins, leukotrienes, and medicine","FirstCategoryId":"1085","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/0262174687900023","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 6

摘要

用G蛋白激活剂氟化钠(NaF)研究了G蛋白和蛋白激酶C在大鼠膀胱中介导肌碱受体相关前列腺素合成中的作用;蛋白激酶C激活剂肉豆蔻酸磷(PMA)和二丁酸磷(PDBU);蛋白激酶C抑制剂H7和拟副交感神经化合物carbachol。NaF体外刺激大鼠膀胱前列环素(PGI2)合成(EC50 = 6 mmol)。−1),EDTA的存在抑制了这一作用(10 mmol。1−1)。苯酚增强了NaF的刺激作用。钙通道阻滞剂维拉帕米、硝苯地平和蛋白激酶C抑制剂H7以浓度依赖性的方式抑制NaF (10 mmol.l−1)刺激的PGI2合成。碳甾醇刺激的PGI2合成也被H7抑制。PDBU和PMA对新生、naf或碳水化合物刺激的膀胱PGI2合成没有影响。NaF对其他前列腺素(PGE2和PGF2α)的刺激程度与PGI2相同,H7和钙通道阻滞剂对其抑制程度相同。二丁基腺苷3 ':5 ' -环单磷酸对新生或naf刺激的前列腺素合成没有影响。由于氟化物激活了G蛋白,这些数据表明:(1)大鼠膀胱中G蛋白介导了毒蕈碱受体-前列腺素合成偶联;(2)氟化作用是由蛋白激酶C介导的,而不是腺苷环化酶,可能是通过磷脂酶C的激活,从而产生蛋白激酶C的激活剂二酰基甘油;(3)活化的蛋白激酶C可能启动与前列腺素合成相关的Ca2++动员;(4)与其他平滑肌相比,磷酸酯对膀胱PGI2合成缺乏影响,这表明在不同的平滑肌组织中存在不同形式的蛋白激酶C。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Fluoride but not phorbol esters stimulate rat urinary bladder prostanoid synthesis: Investigations into the roles of G proteins and protein kinase C

The role of G proteins and protein kinase C in mediating muscarine receptor-linked prostanoid synthesis by the rat urinary bladder was investigated using the G protein activator, sodium fluoride (NaF); the protein kinase C activators, phorbol myristate (PMA) and phorbol dibutyrate (PDBU); the protein kinase C inhibitor, H7, and the parasympathomimetic, carbachol. NaF stimulated in vitro rat urinary bladder prostacyclin (PGI2) synthesis (EC50 = 6 mmol. −1), an action inhibited by the presence of EDTA (10 mmol. 1−1). Carbachol potentiated the stimulatory action of NaF. NaF (10 mmol.l−1)-stimulated PGI2 synthesis was inhibited by the calcium channel blockers verapamil, nifedipine and the protein kinase C inhibitor, H7, in concentrationdependent manners. Carbachol-stimulated PGI2 synthesis was also inhibited by H7. PDBU and PMA were without effect on de novo, NaF-or carbachol-stimulated urinary bladder PGI2 synthesis. Other prostanoids (PGE2 and PGF) were stimulated to the same degree as PGI2 by NaF, and inhibited equally by H7 and calcium channel blockers. Dibutyryl adenosine 3′:5′-cyclic monophosphate was without effect on de novo or NaF-stimulated prostanoid synthesis. Since fluoride activates G proteins, these data indicate that: (1) muscarine receptorprostanoid synthesis coupling is mediated by G proteins in the rat urinary bladder; (2) fluoride action is mediated by protein kinase C and not adenyl cyclase, probably through activation of phospholipase C and therefore the generation of the protein kinase C activator diacyl glycerol; (3) activated protein kinase C may initiate Ca2++ mobilisation linked to prostanoid synthesis; and (4) the lack of effect of the phorbol esters on urinary bladder PGI2 synthesis, in contrast to that on other smooth muscle, indicates that in different smooth muscle tissues there are varying forms of protein kinase C.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信