BIOSYNTHESIS, PROCESSING & SECRETION OF NEUROPEPTIDES & PITUITARY PEPTIDE HORMONE

ACTHI、内啡肽、α-MSH、加压素和催产素的生物合成， 重点研究了参与蛋白质分解的酶。 处理各自的前荷尔蒙。一种激素前转换酶 (PCE)，它特异性地切割成对的碱基 内源性前激素(前阿片黑素皮质素、催产素和 前加压素)为活性激素，已从牛中分离纯化 垂体中间叶和神经叶分泌小泡。提纯的PCE 似乎是相同的，并已被描述为 大约7万个道尔顿糖蛋白。PCE以可溶的膜形式存在 并被发现也能将胰岛素原裂解为胰岛素。一个 羧肽酶B样酶和氨基肽酶B样酶， 从C-和N-末端去除碱性残基的功能， 分别来自多肽激素，在PCE的作用下，有 在中叶和神经叶的分泌小泡中发现。这个 氨基肽酶B类酶的部分纯化和性质 作为一种大于75,000道尔顿金属肽酶。监管 多巴胺和环磷酸腺苷(CAMP)生物合成阿片黑素皮质素原(POMC) 在蟾蜍脑下垂体中间叶进行了研究。药理分析 提示蟾蜍中叶多巴胺受体为D2。 类别，与腺苷环化酶负偶联。因此，多巴胺 在与受体结合后，通过降低细胞内的 CAMP水平，从而导致POMC合成减少 组织。在小鼠体内研究了POMC生物合成的调节。 高渗应激。给动物加盐两天会导致一种 POMC mRNA水平、POMC合成和加工水平增加2-3倍 脑垂体前叶POMC衍生肽的分泌。在……里面 比较POMC来源的POMC的mRNA水平、POMC合成和分泌 中间叶的多肽减少了56%。

The biosynthesis of ACTHI, endorphin, Alpha-MSH, vasopressin and oxytocin, was studied with emphasis on the enzymes involved in the proteolytic processing of the respective prohormones. A prohormone converting enzyme (PCE) which specifically cleaves at paired basic residues oif the endogenous prohormones (pro-opiomelanocortin, prooxytocin and pro-vasopressin) to the active hormones, has been purified from bovine pituitary intermediate and neural lobe secretory vesicles. Purified PCE from both lobes appears to be identical and has been characterized as a about 70,000 dalton glycoprotein. PCE exists in a soluble and membrane associated form and was found to cleave pro-insulin to insulin as well. A carboxypeptidase B-like enzyme and an aminopeptidase B-like enzyme which function to remove the basic residues from the C- and N-terminal, respectively, from the peptide hormone, following the action of PCE, have been found in intermediate lobe and neural lobe secretory vesicles. The aminopeptidase B-like enzyme has been partially purified and characterized as a greater than 75,000 dalton metallopeptidase. The regulation of biosynthesis of pro-opiomelanocortin (POMC) by dopamine and cAMP was studied in the toad pituitary intermediate lobe. Pharmacological analyses indicate that the toad intermediate lobe dopamine receptor is of the D2 category and negatively coupled to adenylate cyclase. Thus the dopamine acts, subsequent to binding to the receptor, by lowering the intracellular cAMP level which then results in a decrease in POMC synthesis in the tissue. The regulation of POMC biosynthesis was also studied in mice under hyperosmotic stress. Salt loading the animals for two days resulted in a 2-3 fold increase in POMC mRNA levels, POMC synthesis and processing and secretion of POMC derived peptides from the anterior pituitary. In contrast POMC mRNA levels, POMC synthesis and secretion of POMC derived peptides were decreased by 56% in the intermediate lobe.