MOLECULAR CHARACTERIZATION OF H2 RECEPTOR DUAL SIGNALING

描述（改编自研究者摘要和/或目的）：这是 重新提交研究分子机制的申请， 组胺H2受体与cAMP偶联的生物学意义 和钙信号通路。 H2受体与cAMP的偶联 组胺H2受体通路已建立;然而，组胺H2受体相关 细胞内钙离子的升高是最近才出现的， 1986年在兔子的壁细胞中观察到。 这一观察结果现已 在包括狗和类似数据在内的几个物种中得到证实 在HL 60细胞中，许多研究表明， 证明了cAMP途径与增加的 盐酸分泌;然而，组胺的生理相关性 与壁细胞中的钙信号通路的偶联尚未被发现。 确立了习 在1991年克隆H2受体之后，申请人 与山田博士及其同事合作证明， 将H2受体转染到HEPA细胞中导致H2受体 偶联腺苷酸环化酶/cAMP和磷脂酶C/钙/肌醇 三磷酸（IP 3）信号通路。 具体目标是 建议继续这方面的调查如下：1） 表征H2受体的结构组分， 使用嵌合H2受体与两种途径相关联， 基于受体的合成肽; 2）表征G蛋白 参与原发性和转化性的双重信号通路 （3）根据前两个具体的知识， 目的是利用H2受体/G蛋白靶向寡肽、抗血清 和反义探针来确定双重基因的相对重要性 壁细胞分泌活动的信号机制。 自H2以来 受体活化也调节许多生物多样性 不同细胞类型的反应，了解其功能是 具有广泛的生物学意义。

DESCRIPTION (adapted from investigator's abstract and/or aims): This is a resubmission of an application to study the molecular mechanisms and biological significance of histamine H2 receptor coupling to both cAMP and calcium signaling pathways. Coupling of the H2 receptor to the cAMP pathway is well established; however, histamine H2-receptor associated elevation of intracellular calcium is more recent, having been first observed in rabbit parietal cells in 1986. This observation has now been confirmed in several species including dog and similar data published for HL60 cells.In the parietal cell, numerous studies have demonstrated a clear association between the cAMP pathway and increased HCl secretion; however, the physiological relevance of histamine coupling to the calcium signaling pathway in parietal cells has not been established. Following the recent cloning of the H2 receptor in 1991, the applicant in collaboration with Dr. Yamada and colleagues demonstrated that stable transfection of the H2 receptor into HEPA cells resulted in H2 receptor coupling to adenyl cyclase/cAMP and phospholipase C/calcium/inositol triphosphate (IP3) signaling pathways. The specific aims of this proposal are to continue this line of investigation as follows: 1) To characterize the structural components of the H2 receptor that are linked to the two pathways using chimeric H2 receptors in concert with receptor based synthetic peptides; 2) To characterize the G-proteins involved in dual signaling pathways in both primary and transformed cells; 3) On the basis of knowledge gained from the first two specific aims, to utilize H2 receptor/G-protein-targeted oligopeptides, antisera and antisense probes to determine the relative importance of the dual signaling mechanism in parietal cell secretory activity. Since H2 receptor activation also modulates a number of biologically diverse responses in different cell types, an understanding of its function is expected to have broad biological significance.