CHEMISTRY AND BIOLOGY OF GUT PANCREASTATIN

胰抑素，一种新的49个氨基酸的多肽 从猪胰腺中提取，已经显示出抑制葡萄糖 刺激生长抑素和胰岛素释放从分离的 灌注胰腺。 胰抑素的这些作用，加上 其在胃粘膜中的定位（Tatemoto;个人 交流），促使我们研究这种肽对 胃壁细胞 我们的初步研究表明， 胰抑素直接抑制胃泌素、卡巴胆碱、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，胰抑素可能 在调节胃酸分泌方面具有生理重要性 通过独特的机制。 这一背景是 为了进行拟议的研究， 胰蛋白酶抑制剂在胃肠道中的生物化学。 初始 将努力制定一个敏感和具体的 抗胰蛋白酶抑制素的抗体，其将用于表征 免疫组化检测肠组织中的肽， 放射免疫法 由于我们先前已经观察到， 胰抑素的生物活性在于羧基末端， 我们将利用十七肽的肽连接到 以甲状腺球蛋白为免疫原， 家兔 将犬肠胰蛋白酶抑制素纯化，并将其氨基化， 确定酸序列，以便将物种特异性肽 可用于生理学研究。 胰蛋白酶抑制剂对 将在体内检查犬的胃酸分泌， 胃瘘与生长抑素和胃泌素分泌 将在分离的灌注大鼠中研究对肽的反应 肚子 胰抑素作用的细胞基础是 在离体犬胃壁的制备物中测定， 生长抑素和胃泌素细胞。 胰抑素的动力学 将使用125 I标记的 胰抑素类似物作为配体。 的信号转导 因此，激活的途径将通过测量 cAMP、PI周转和膜相关蛋白激酶 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.