PHYSIOLOGY OF HYPOTHALAMIC NEUROHORMONES

下丘脑神经激素的生理学：一种新的下丘脑神经激素 从绵羊下丘脑中分离得到一种含38个氨基酸残基的神经肽 组织的腺苷酸环化酶刺激活性 垂体细胞培养 测定了氨基酸序列， 发现合成肽与天然肽一样具有活性， 腺苷酸环化酶刺激活性（阿克萨）。缩短的 随后分离出具有27个残基的形式，并发现其为 活性为38个残基的肽。 这些肽被命名为PACAP 38 （具有38个残基的垂体腺苷酸环化酶激活多肽）和 PACAP 27，分别。 这两种肽都具有酰胺化的 C端 虽然这些肽是基于它们的阿克萨分离的， 在垂体细胞中，它们的生理作用仍然未知。 因此，我们建议研究它们在 垂体细胞功能使用PACAP的合成制剂。 的 这项研究的直接目标是确定垂体靶细胞， 用组织化学和免疫组织化学方法对大鼠PACAP进行研究。 然后我们将检查PACAP是否符合生理学要求， 促垂体激素 要求包括：（i） 外层免疫阳性神经纤维的密集网络 正中隆起;（ii）肽对垂体的直接作用 细胞和在这些细胞中存在特异性高亲和力结合位点 (iii)垂体门静脉血中PACAP浓度较高 比在外周血;（iv）澄清的终点， PACAP在垂体细胞中的作用。 如果PACAP是一种生理性的 脑下垂体的调节器，负反馈或正反馈 机制可能是垂体和PACAP神经元之间的相互作用， 下丘脑 这个问题将使用 免疫组化、肽测定RIA和PACAP mRNA 在不同的实验条件下，下丘脑。 的 PACAP的生理作用也将由 内源性PACAP作用的免疫中和。

PHYSIOLOGY OF HYPOTHALAMIC NEUROHORMONES: A novel hypothalamic neuropeptide with 38 residues was isolated from ovine hypothalamic tissues based on its activity of adenylate cyclase stimulation in rat pituitary cell culutres. The amino acid sequence was determined and the synthetic peptide was found to be as active as the native peptide in terms of adenylate cyclase stimulating activity (ACSA). The shortened form with 27 residues was subsequently isolated and found to be as active as the 38 residue peptide. These peptides were named PACAP38 (Pituiary Adenylate Cyclase Activating Polypeptide with 38 residues) and PACAP27, repectively. Both of these peptides possessed amidated C-terminus. Although these peptides were isolated based on their ACSA in the pituitary cells, their physiological role remains unknown. Therefore, we propose to investigate their regulatory role in the pituitary cell function using synthetic preparations of PACAPs. The immediate goal of the study is to determine the pituitary target cells for PACAP using histochemical and immunohistochemical method in rats. Then we will examine if PACAP meets the requirement for a physiological hypophysiotropic hormone. The requirement includes (i) presence of dense net-work of immunopositive nerve fibers in the external layer of the median eminence; (ii) direct action of the peptide on the pituitary cells and presence of specific high affinity binding site in these cells (iii) greater concentration of PACAP in the hypophysial portal blood than in the peripheral blood; (iv) clarification of the end point of the action of PACAP in the pituitary cells. If PACAP is a physiological regulator of the pituitary gland, a negative or positive feed-back mechanism may interplay between the pituitary and PACAP neurons in the hypothalamus. This problem will be investigated using immunohistochemistry, RIA for determination of peptide, and PACAP mRNA in the hypothalamus under various experimental conditions. The physiological actions of PACAP will also be examined by the immnunoneutralization of the action of endogenous PACAP.