Immunocytochemical localization in rat brain of a prolactin release-inhibiting sequence of gonadotropin-releasing hormone prohormone

The structure of a precursor protein for gonadotropin-releasing hormone (GnRH) of relative molecular mass 10,000 has recently been deduced from cloned complementary DNA sequences derived from human placental messenger RNA. The 56-amino-acid peptide representing residues 14-69 of this prohormone exhibits potent inhibition of prolactin secretion. To investigate whether the same prohormone is synthesized in mammalian brain and describe the anatomical distribution of the prolactin-inhibiting region of this molecule, we have generated antiserum to a synthetic peptide containing residues 40-53 of the human placental precursor. We report here that a substance recognized by this antibody is present in GnRH-containing neurones of the rat brain and appears to coexist with GnRH in secretory granules of nerve terminals in the median eminence. These results indicate homology between hypothalamic and placental prohormones for GnRH and are consistent with the suggestion elsewhere in this issue that a prolactin-inhibiting factor (PIF) is generated from this prohormone and cosecreted with GnRH by nerve terminals in the median eminence.     

A prolactin-inhibiting factor within the precursor for human gonadotropin-releasing hormone

The cloned complementary DNA sequence encoding the human gonadotropin-releasing hormone (GnRH) precursor protein was used to construct an expression vector for the bacterial synthesis of the 56-amino acid GnRH-associated peptide (GAP). GAP was found to be a potent inhibitor of prolactin secretion and to stimulate the release of gonadotropins in rat pituitary cell cultures. Active immunization with peptides corresponding to GAP sequences led to greatly increased prolactin secretion in rabbits.     

Growth of human breast cancer cells inhibited by a luteinizing hormone-releasing hormone agonist

About one-third of human breast cancers require hormones for their continued growth and endocrine ablation or anti-hormone therapy can cause regression of these tumours. As a consequence, ovariectomy in premenopausal women or administration of an anti-oestrogen (tamoxifen) in postmenopausal women represent major options for treatment of metastatic breast cancer. Alternatively, chronic administration of agonistic analogues of luteinizing hormone-releasing hormone (LHRH) causes regression of mammary tumours in experimental animals, and such treatment has shown promise in a small series of premenopausal women with advanced breast cancer. It has been assumed that these results were achieved by suppressing the pituitary-ovarian axis, as the treatment causes a reduction in circulating levels of gonadal steroids similar to that produced by castration. However, LHRH agonists can exert major effects on tissues other than the pituitary in animals and in the human. Such findings, coupled with reports of LHRH in human breast milk and immunohistochemical evidence for the presence of LHRH-like activity in some human breast tumours, prompted us to test whether LHRH agonists could have direct antitumour effects. We now report major direct effects of LHRH and its agonists on the growth of breast tumour cells in culture.     

无限厚靶向理想薄靶的转换

提出了一种简单的背散射自理方法，将无限厚靶转换成理想薄膜，该方法无需模拟背散射谱的形状，即可求出未知样品中各万分的相对含量，对于卢瑟福散射和弹性共振散射同样有效。并用氧化铜和氧化钛混合配制了系列标样予以检验，结果与参考值很好地符合。     

Coupling of agonist binding to channel gating in an ACh-binding protein linked to an ion channel

Neurotransmitter receptors from the Cys-loop superfamily couple the binding of agonist to the opening of an intrinsic ion pore in the final step in rapid synaptic transmission. Although atomic resolution structural data have recently emerged for individual binding and pore domains, how they are linked into a functional unit remains unknown. Here we identify structural requirements for functionally coupling the two domains by combining acetylcholine (ACh)-binding protein, whose structure was determined at atomic resolution, with the pore domain from the serotonin type-3A (5-HT3A) receptor. Only when amino-acid sequences of three loops in ACh-binding protein are changed to their 5-HT3A counterparts does ACh bind with low affinity characteristic of activatable receptors, and trigger opening of the ion pore. Thus functional coupling requires structural compatibility at the interface of the binding and pore domains. Structural modelling reveals a network of interacting loops between binding and pore domains that mediates this allosteric coupling process.     

脊椎动物促性腺激素释放激素的结构、基因表达与调控的研究进展

综述了有关对脊椎动物促性腺激素释放激素的结构、基因表达与调控的研究进展 .阐明促性腺激素释放激素结构多样性 ,功能多样性 ,及其基因表达与调控 ,并对可能的应用前景作简要阐述     

管式反应器中环己烯氧化制环氧环己烷

以过氧化氢为氧化剂,自制的十六烷基吡啶过氧磷钨酸为催化剂催化环己烯合成环氧环己烷,根据釜式反应器反应的最佳时间确定了管式反应器的管长,考察了反应温度、环己烯与H₂O₂物质的量比、反应溶液的pH和催化剂用量对产物收率的影响,并对这些条件进行了优化。实验结果表明,管式反应器最佳条件为反应温度50℃,反应时间30 min,投料比n（环己烯）：n（H₂O₂）：n（催化剂）：n（氯仿）=1：0.75：0.000 25：2,pH=3,此条件下环氧环己烷的收率可达55.24%。同样实验条件下釜式反应器内环氧环己烷收率为44.42%。     

Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist

The parasympathetic branch of the autonomic nervous system regulates the activity of multiple organ systems. Muscarinic receptors are G-protein-coupled receptors that mediate the response to acetylcholine released from parasympathetic nerves. Their role in the unconscious regulation of organ and central nervous system function makes them potential therapeutic targets for a broad spectrum of diseases. The M2 muscarinic acetylcholine receptor (M2 receptor) is essential for the physiological control of cardiovascular function through activation of G-protein-coupled inwardly rectifying potassium channels, and is of particular interest because of its extensive pharmacological characterization with both orthosteric and allosteric ligands. Here we report the structure of the antagonist-bound human M2 receptor, the first human acetylcholine receptor to be characterized structurally, to our knowledge. The antagonist 3-quinuclidinyl-benzilate binds in the middle of a long aqueous channel extending approximately two-thirds through the membrane. The orthosteric binding pocket is formed by amino acids that are identical in all five muscarinic receptor subtypes, and shares structural homology with other functionally unrelated acetylcholine binding proteins from different species. A layer of tyrosine residues forms an aromatic cap restricting dissociation of the bound ligand. A binding site for allosteric ligands has been mapped to residues at the entrance to the binding pocket near this aromatic cap. The structure of the M2 receptor provides insights into the challenges of developing subtype-selective ligands for muscarinic receptors and their propensity for allosteric regulation.     

Dihydroouabain is an antagonist of ouabain inotropic action

The Na+, K+-pump controls a wide variety of cellular systems and its inhibition by cardiac glycosides modifies important physiological functions and evokes several pharmacological effects (refs 1, 2 and refs therein). However, not all the actions of cardiac glycosides can be attributed to Na+, K+-pump inhibition and several observations show that, at low doses, cardiac glycosides stimulate the pump. It has been proposed that their positive inotropic effect could be the sum of two processes: the inhibition of the pump and a still unknown additional inotropic mechanism. In guinea pig heart, low doses of ouabain interact with high-affinity binding sites, which differ from the lower-affinity sites responsible for Na+, K+-pump inhibition. It has been suggested that ouabain interaction with these high-affinity sites could be responsible for the additional inotropic mechanism. The existence of two classes of ouabain-binding sites has been documented not only in guinea pig heart, but also in dog, rat and human heart. Dihydroouabain, a derivative of ouabain in which the lactone ring is saturated, is about 50-fold less potent than ouabain as an inhibitor of Na+, K+-pump and does not stimulate the pump at low doses. Its inotropic effect can be entirely accounted for by the inhibition of the pump. We have examined the pharmacological action of ouabain in the presence of dihydroouabain and report here that dihydroouabain reduces ouabain inotropic action but not Na+, K+-pump inhibition.     

一种实用的模数转换A／D板的研制

本文较详细地介绍了所设计的Ａ／Ｄ板的硬件组成及应用软件。实践证明：该板是最廉价的又是最实用的。