Interaction of opioid peptides and other drugs with multiple kappa receptors in rat and human brain. Evidence for species differences.

Previous experiments resolved four kappa binding sites in guinea pig brain termed kappa 1a, kappa 1b, and kappa 2b. The present study was undertaken to examine the occurrence of kappa receptor subtypes in rat and human brain. [3H]U69,593 and [3H]bremazocine were used to label kappa 1 and kappa 2 binding sites, respectively, present in brain membranes depleted of mu and delta binding sites by pretreatment with the irreversible ligands, BIT and FIT. Low levels of [3H]U69,593 binding precluded a detailed quantitative study of kappa 1 binding sites in these species. Quantitative examination of [3H]bremazocine binding resolved two kappa 2 binding sites in both rat and human brain whose ligand selectivity patterns differed from that of the guinea pig. These observations suggest that there may be considerable variation in the ligand recognition site of kappa receptor subtypes among mammalian species.     

豚鼠肠系膜下神经节细胞电活动与结肠运动的关系

在豚鼠肠系膜下神经节(IMG)及其支配的结肠段联合标本上,对IMG细胞内电位与肠段纵肌或环肌舒缩活动进行了同步记录。实验结果表明:(1)肠段预置张力为零时,约50％IMG细胞有自发的快兴奋性突触后电位(EPSP)活动,切断结肠神经或以筒箭毒(50μmol/L)灌流IMG后消失;(2)筒箭毒或低钙高镁溶液阻断神经节传递时,环肌节律性收缩幅度增大,节律变慢,但对纵肌节律性收缩无明显影响,(3)串刺激节前神经,在IMG细胞引起一串快EPSP或动作电位并常跟随迟慢的EPSP,同时,纵肌在0.1-0.2s潜伏期后出现迅速的、时程基本与动作电位串一致的舒张波,后者在筒箭毒灌流IMG后消失,而环肌运动可见舒张、舒张波延长或收缩波增大。结果提示:IMG不仅中继经典的胆碱能传出功能,还参与以胆碱能传递为中介的肠-肠反射,该反射活动的传出效应主要在于抑制环肌收缩。     

人酸性成纤维细胞生长因子神经营养作用的初步研究

本实验研究了人酸性成纤维细胞生长因子(haFGF)的体外神经营养作用。结果表明,haFGF在体外能明显促进鸡胚(E-8)脊髓组织神经突起的生长,并能明显改变新生大鼠脑星形胶质细胞的形态,使扁平、多角形紧密联接的细胞转化为具有纤维样突起的胶质细胞,同时对胶质细胞DNA合成也有一定促进作用。实验还证明,haFGF可增加体外培养新生大鼠海马神经元的存活,且大大增加神经元胞体体积及突起长度。     

内皮素对大鼠肠系膜微血管的作用

应用显微电视录象技术可观察到内皮素(ET)对戊巴比妥钠麻醉的 Wistar 大鼠的肠系膜微血管有收缩作用,血液流速减慢,甚至产生微循环障碍,这个作用相当持久,并呈剂量依赖关系。ET 的这个作用远高于去甲肾上腺素。这些结果提示,ET 作为强烈的微血管收缩剂,在微循环紊乱疾病的发病学中可能具有重要意义。     

Catalytic properties of chloroplast F1-ATPase modified at catalytic or noncatalytic sites by 2-azido adenine nucleotides

When heat-activated F1-ATPase from chloroplasts was repeatedly exposed to Mg2+ and 2-azido-ATP, followed by separation from medium nucleotides and photolysis, a total of two sites per enzyme, both catalytic and noncatalytic, were labeled. In a coupled assay with pyruvate kinase about half the activity was lost when one site per enzyme was modified. However, increased modification resulted in no further loss of activity. In contrast, methanol-sulfite activation of the enzyme showed a loss of most of the catalytic capacity when one site per enzyme was modified. Predominant labeling of either one catalytic or one noncatalytic site caused a loss of most of the activity in either assay. An indication that the enzyme modified at one site retained some catalytic activity was verified by measurement of the [18O]Pi species formed when [gamma-18O]ATP was hydrolyzed by partially derivatized enzyme. With either catalytic or noncatalytic site modification, the distributions of [18O]Pi species formed showed that the modified enzyme had different catalytic characteristics. An interpretation is that with modification by azido nucleotides at either catalytic or noncatalytic sites, capacity for rapid catalysis is largely lost but the remaining sites retain weak modified catalytic properties.     

Cross-reactive cellular and humoral immunity to carcinogen-induced chicken fibrosarcomas. I. Protective cross-immunity between transplantable tumor lines

Dimethylbenz[a]anthracene (DMBA)-induced transplantable fibrosarcomas in B2 homozygous chickens (SC line) grow progressively in normal chickens, but are rejected by chickens immunized previously with irradiated tumor cells and Corynebacterium parvum. Tumor-immune chickens resist challenge by the immunizing tumor lines as well as by some, but not all, fibrosarcoma lines. The pattern of cross-reactivity between four DMBA-induced transplantable tumor lines was examined in detail. Ability to reject a tumor challenge correlated very well (p less than 0.001) with the presence of delayed-type hypersensitivity (DTH) to that tumor. Immunization with one of two of the DMBA-induced lines tested also caused rejection of transplantable tumors developed from methylcholanthrene-induced and benzo(a)pyrene-induced primary fibrosarcomas. Although immunization with tumor caused DTH to chicken embryo fibroblasts (CEF), immunization with CEF failed to cause protective immunity or DTH to tumors. Presence of protective immunity, where tested, also correlated with the ability of spleen cells from immune donors to inhibit tumor growth in Winn tests. Humoral immunity exhibited even greater cross-reactivity than did cellular immunity. Distinct patterns of cross-reactivity were nevertheless observed with respect to the serum antibodies as detected in ELISA. Two of these patterns were also observed in several sera from primary tumor-bearing chickens, both including reactivity with CEF. Such reactivity was absent from normal chicken sera.     

In vivo and in vitro studies on the segregation of autonomic and sensory cell lineages

Analysis of interspecific quail/chick chimaeras (made by grafting neural primordium from one species to the other) has demonstrated that the neural crest cell population, which gives rises to a large number of derivatives, including the great majority of peripheral ganglion cells, is pluripotential. When peripheral ganglia themselves are transplanted, it can be shown that many of the developmental potentialities of the parent structure are retained, their ultimate expression depending on the microenvironment in which they become located. One of the conclusions obtained from these in vivo studies, that sensory ganglia contain dormant precursors with autonomic potentialities, has been confirmed and extended by the results of in vitro investigations with dissociated 9- to 15-day embryonic quail dorsal root ganglia. Undetectable during normal embryonic development, adrenergic properties (tyrosine hydroxylase immunoreactivity, radio- and cytochemically demonstrable catecholamine production) develop in a population of small, multipolar cells after four days in culture. This differentiation is strongly dependent on the presence of chick embryo extract in the medium. Unlike the postmitotic primary sensory neurons of the ganglia, many of the adrenergic cells were found to incorporate 3H-thymidine during the culture period. These results support the contention that the latent autonomic percursors belong to the non-neuronal compartment of sensory ganglia.     

Regulation of methyl group metabolism in lactating ewes

The effect of lactation on a number of enzymes involved in transmethylation reactions and the secretion of major methyl compounds into milk have been examined in sheep. The activities of hepatic phospholipid methyltransferase and 5-methyltetrahydrofolate-homocysteine methyltransferase were significantly higher in lactating ewes, compared with those in non-lactating ewes, while the activity of both hepatic and pancreatic glycine methyltransferase was significantly lower in the lactating state. No differences were observed in the activities of hepatic guanidoacetate methyltransferase, betaine-homocysteine methyltransferase and cystathionine beta-synthase on lactation. These results suggest that the extra demand for methyl groups for the secretion of methyl compounds in the milk is facilitated by enhancing the rate of de novo methyl group synthesis and lowering the rate of physiologically nonessential methylation.