选择性κ阿片激动剂K-Ⅱ与U-50488的药理作用比较

K-Ⅱ系k阿片激动剂U-50488的同类物。通过部分离体和整体实验比较了K-Ⅱ与U-50488的药理作用。实验发现,K-Ⅱ抑制电刺激兔输精管收缩的IC₅₀值为0.42 nmol/L,U-50488为26.5 nmol/L;K-Ⅱ抑制小鼠运动功能(横筛法)的ED₅₀值为1.7 mg/g,U-50488为15.3 mg/kg;K-Ⅱ的小鼠LD₅₀值为152.5 mg/kg,U-50488为118.4 mg/g;K-Ⅱ明显降低小鼠自发活动的作用比U-50488强5倍。结果表明,K-Ⅱ是一个药理作用较U-50488强的k受体激动剂。     

Effect of acute inflammation on rat apolipoprotein mRNA levels

Hybridization studies using specific cDNA have been used to determine the mRNA levels for rat apolipoproteins AI, AII, AIV, and E in extracts of rat liver and intestine. The ratios of intestinal mRNA/liver mRNA for apolipoprotein AI (apo AI), apo AIV, and apo E were 1.3, 1.7, and 0.1, respectively. Apo AII mRNA was detected in the liver but not in the intestine. The mRNA levels for apo AII and apo AIV in rat liver decreased during inflammation to minimums of 40% and 25% of normal, respectively. The mRNA levels for apo AIV in the intestine, apo E in the liver and for apo AI in both the liver and intestine did not change significantly during inflammation. The time course for the decrease in the hepatic mRNA levels for apo AIV was similar to those previously observed for the negative acute-phase proteins albumin and transthyretin. The serum levels for apo AIV were not affected by inflammation.     

Cyclic nucleotide phosphodiesterase isozymes in neuroblastoma cells

Adenosine 3',5'-cyclic monophosphate (cAMP) content of neurons is determined not only by the rate of synthesis but also by the rate of hydrolysis by cyclic nucleotide phosphodiesterases. Multiple forms of cyclic nucleotide phosphodiesterase exist in brain and other tissues, and these may be regulated by various hormones and neuromodulators. The present study examines this regulation in a cloned line of neuroblastoma cells (N18TG2). A biphasic Lineweaver-Burk plot of cAMP hydrolysis revealed two Kms approximating 5 and 25 microM. Lineweaver-Burk plots of cGMP hydrolysis were linear over a range of 1 microM to 1 mM and exhibited a Km of 37 microM. Neither cAMP nor cGMP competed for hydrolysis of the alternative cyclic nucleotide. No evidence for an allosteric activation of cAMP phosphodiesterase by cGMP was found. Calcium regulation of phosphodiesterase was not found in spite of preparation of the cell extract with several protease inhibitors, and addition of exogenous calmodulin. No effect of calmodulin antagonists (calmidazolium, W7, or trifluoperazine) was observed in vitro or in situ. Growth of the cells in the presence of 200 nM 3,5,3'-triiodothyronine (T3) resulted in an increased hydrolysis of cAMP but of cGMP. This increase was attributed to an increase in Vmax with no change in either high or low Km. This response was blocked by cycloheximide, suggesting that the thyroid hormone effect requires protein synthesis. The thyroid hormone response in neuroblastoma cells is compared with the results of other studies of thyroid hormone effects on phosphodiesterase in other tissues in vivo.     

Effects of cigarette smoking and dietary lipids on rat lipoprotein metabolism

The effects of cigarette smoke inhalation on rat lipoprotein metabolism have been examined. Rats were subjected to cigarette smoke exposure over a 3-week period (two 1-h sessions/day) using a Bat-Mason inhalation machine. Rats exposed to cigarette smoke showed a decrease in total serum triglyceride and an increase in very low density lipoprotein cholesterol (VLDL-C). Administration of cigarette smoke to rats fed a saturated fat and cholesterol enriched diet also led to an increase in VLDL-C and a decrease in total serum triglycerides compared to controls. In addition, cigarette smoke exposure to animals fed the lipid enriched diet caused a decrease in high density lipoprotein cholesterol (HDL-C). Pair-feeding experiments indicated that the increase in VLDL-C and the decrease in HDL-C could not be solely attributed to the reduction in food intake and the small decrease in growth rate observed following cigarette smoke exposure. The changes observed in VLDL-C and HDL-C are at least qualitatively similar to the changes seen in human smokers compared to non-smokers.     

用气相色谱研究抗氧化剂对膜脂肪酸的保护作用

本文应用气相色谱技术直接测定三种生物膜(人红细胞膜,人血小板膜和鼠肝线粒体膜)多不饱和脂肪酸的含量变化,检测脂质过氧化程度。实验证实几种多羟酚类化合物(儿茶精,阿魏酸钠和没食子酸及其衍生物)不同程度地抑制(OH)诱导的脂质过氧化反应,并呈量效和构效关系。这类抗氧化剂对保护生物膜的结构与功能是有益的。