CHEMISTRY AND BIOLOGY OF GUT PANCREASTATIN

一种新分离的49个氨基酸的多肽--胰腺抑素 从猪胰腺中提取的，已被证明能抑制血糖 体外刺激的生长抑素和胰岛素的释放 灌流的胰腺。胰抑素的这些作用，加上 它在胃粘膜中的定位(纹身；个人 通信)，促使我们研究这种多肽对 胃壁细胞。我们的初步研究表明 胰抑素直接抑制胃泌素、氨基甲胆碱、组胺和 二丁酰cAMP刺激顶叶活动的方式 增强生长抑素的作用。因此，胰抑素可以 在调节胃酸分泌方面具有生理意义 通过独特的机制。这一背景是本文的基础。 对于拟议的研究，以检查生理学和 胰抑素在胃肠道中的生物化学。首字母 将努力制定一种敏感和具体的 抗胰腺抑素抗体将被用来表征 免疫组织化学和免疫组织化学方法检测肠道组织中的多肽 放射免疫分析。因为我们之前已经观察到 胰抑素的生物活性位于羧基末端， 我们将利用与之相关联的肽的十七肽 甲状腺球蛋白作为免疫原提高小鼠多克隆抗血清的研究 兔子。犬肠道胰抑素将被提纯，其氨基 确定了酸序列，以使物种特异性多肽 可用于生理学研究。胰岛抑素对血管紧张素转换酶的影响 胃酸分泌将在体内检测狗的胃酸分泌 胃瘘与生长抑素和胃泌素的分泌 对该多肽的反应将在分离的灌流大鼠中进行研究 胃。胰抑素作用的细胞基础将是 在离体犬胃壁制备中测定， 生长抑素和胃泌素细胞。胰抑素的动力学研究 将使用125I标记的方法检测与壁细胞的结合 胰抑素类似物作为配基。信号转导 这样激活的通路将通过以下测量进行评估 环磷酸腺苷、磷脂酰肌醇转换率与膜相关蛋白激酶 C活动。

Pancreastatin, a novel 49 amino acid peptide recently isolated from porcine pancreas, has been shown to inhibit glucose stimulated somatostatin and insulin release from the isolated perfused pancreas. These actions of pancreastatin, coupled with its localization in the gastric mucosa (Tatemoto; personal communication), prompted us to examine this peptide's effect on gastric parietal cells. Our preliminary studies indicate that pancreastatin directly inhibits gastrin, carbachol, histamine and dibutyryl cAMP stimulated parietal activity in a fashion that augments the effect of somatostatin. Thus pancreastatin may have physiological importance in regulating gastric acid secretion through unique mechanisms. This background serves as the basis for the proposed studies to examine the physiology and biochemistry of pancreastatin in the gastrointestinal tract. Initial efforts will be directed at developing a sensitive and specific antibody against pancreastatin which will be used to characterize the peptide in gut tissues by immunohistochemistry and radioimmunoassay. Since we have previously observed that biological activity of pancreastatin rests in the carboxyl terminus, we will utilize the heptadecapeptide of the peptide linked to thyroglobulin as immunogen for raising polyclonal antisera in rabbits. Canine gut pancreastatin will be purified and its amino acid sequence determined so that species specific peptide will be available for physiological studies. The effect of pancreastatin on gastric acid secretion will be examined in vivo in dogs with gastric fistulas and the somatostatin and gastrin secretory response to the peptide will be studied in isolated perfused rat stomachs. The cellular basis for pancreastatin action will be determined in preparations of isolated canine gastric parietal, somatostatin, and gastrin cells. The kinetics of pancreastatin binding to parietal cells will be examined using 125I-labeled pancreastatin analogues as ligand. The signal transduction pathways thus activated will be assessed via measurements of cyclic AMP, PI turnover, and membrane associated protein kinase C activity.