The Mucosecretion in the Submandibular Gland and the Role of Platelet-Activating Factor.

颌下腺的粘液分泌和血小板激活因子的作用。

基本信息

批准号：
62570834
负责人：
DOHI Toshihiro
金额：
$ 1.22万
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：
1987
资助国家：
日本
起止时间：
1987 至 1988
项目状态：
已结题

项目摘要

Adrenergic and cholinergic stimulation of mucin release and platelet-activating factor (PAF) production and the role of Ca^<2+> have been investigated in the isolated dog submandibular gland cells.Stimulation of muscarinic cholinergic, alpha-adrenergic and beta-adrenergic receptors elicited mucin release from dispersed dog submandibular gland cells. The secretory response to Ach was much pronounced than those to adrenergic agonists, and largely dependent on the presence of extrace llul) Ca^<2+>, but the dependency on the extracellular Na^+ was slight. Ionomycin also stimulated mucin release from the cells. Neither muscarinic cholinergic agonists nor ionomycin were effective mucosecretagogues as beta-adrenergic agonists in rat submandibular gland cells. alpha-adrenoceptor-mediated release was decreased by chelating extracellular Ca^<2+> with EGTA. beta-adrenoceptor-mediated response was diminished by extensive exposure of cells to EGTA, due at least in part to the requirement of Ca^<2+> … More for -adrenocetor stimulation of cAMP formation. 8-br-cAMP stimulated ^<45>Ca^<2+> release from the cells preloaded with ^<45>Ca^<2+>.8-br-cAMP-induced mucin release was eliminated in ionomycin-pretreated cells. But not inhibited by chelating extracellular Ca^<2+> and by the treatment of the cells with TMB-8 or in the cells loaded with BAPTA. These results suggest that not only adrenergic system but also muscarinic cholinergic system may participate in the regulation of mucin release in dog submandibular gland, and also provide the possibility that, in addition to cAMP mediated mechanism, Ca^<2+>-dependent mechanisms may be involved in the mucosecretion in dog submandibular acini.Isolated dog submandibular gland cells synthesize platelet-activating factor (PAF) when stimulated with ACh. This production of PAF was concentration- and time-dependent, and was inhibited by pretreatments with anticholinergic agents. PAF accumulated in cells through prior stimulation with ACh vanished rapidly with the addition of atropine. Phenylmethylsulfonylfluoride produced an accumulation of PAF in non-stimulated cells and greatly potentiated further ACh-induced accumulation. PAF production and [^<14>C] arachidonic acid (AA) liberation induced by ACh were increased by higher concentrations of extracellular Ca^<2+>, and ACh failed to stimulate PAF formation in the absence of Ca^<2+>, though ACh still stimulated the liberation of [^<14>C] AA without Ca^<2+>. Both the calcium ionophor ionomycin in intact cells and Ca^<2+> (at concentrations <greater than or equal> 30 nM) in digitonin-permeabilized cells facilitated PAF formation. Lyso-PAF : acetyl-CoA acetyltransferase activity rapidly increased in cells incubated with ACh or ionomycin. These results suggest, at least, that the stimulation of a remodeling pathway is involved in the increased PAF synthesis induced by ACh. Dithiothreitol-insensitive cholinephosphotransferase activity was also activated by ACh. However, the activation of both enzymes by ACh was transient, in spite of the fact that ACh-stimulated PAF formation was continuous. This may suggest that additional mechanism (s) other than the activation of these enzymes play an important role in controlling PAF synthesis. The present study provides further evidence that exocrine submandibular gland cells of dogs have the capacity to increase PAF turnover upon stimulation in a Ca^<2+>-dependent manner and retain PAF within the cells partly associated with the membrane and partly released in the cytosol. Less

肾上腺素和铂激活（PAF）产生的肾上腺素能和胆碱能刺激以及Ca^<2+>在孤立的狗的下颌骨细胞中的作用。刺激毒蕈碱胆碱能，α-肾上腺腺能和辅助接收器的α-分泌率更大，依赖于ca^<2+>的ca <2+>也刺激了细胞中的粘膜。通过细胞暴露于EGTA>的降低，用于cAMP形成的 - 肾上腺刺激刺激8- Br -camp刺激^<45> Ca^<2+> 8-BR训练会引起的MUS被螯合，但通过TMB-8的细胞处理而抑制了细胞。 System May May Participate in The Regulation of Mucin Release in Dog Submandibular Gland, And ALSO PROVIDE THAT, in Addition to Camp Mediated Mechanism, Ca^<2+> N Dog Submandibular Accini.isolated Dog submandibular gland gells synthesize Platelet-Activating Factor (PAF当ACH刺激时，PAF的产生是浓度和时间依赖的，并通过抗胆碱能的抑制作用，通过抗胆碱能力迅速使用抗刺激性细胞。 - 在没有Ca^<2+>的情况下，通过更高的细胞外Ca^<2+>收缩，尽管ACH仍刺激LS的解放和Ca^<2+>（在浓度大于或等于30时NM）在渗透性的细胞中，促进了PAF的形成。但是，通过ACH激活，尽管ACH刺激的PAF形成是连续的，但与这些酶的激活相比，这两种酶是瞬时的提供了进一步的证据，表明狗的外分泌下颌细胞以Ca^<2+>依赖性方式刺激后具有Caprease PAF转换率，并将PAF保留在与膜的部分相关的细胞内，并在细胞质中部分相关。