AIM To investigate the effects of the novel compound pivanampeta on the fatty liver induced by cholesterol-feeding in rabbits and quails. METHODS ①24 male rabbits were divided into four groups randomly as following: control group, model group, pivanampet 1 and 5 mg?kg -1 groups. The serum levels of total cholesterol were determined after the rabbits were cholesterol-fed for 12 weeks. The morphological changes of liver were observed. The levels of cholesterol and malonal-dialdehyde and the activities of glutatione peroxidase in the homogenate of liver were also measured.②181 male quails were divided into six groups randomly:control group, model group, Simvastatin 5 mg?kg -1 group, pivanampet 3,6 and 9 mg?kg -1 groups. The serum levels of total cholesterol were determined after the quails had been fed with cholesterol diets for 11 weeks. After 14 weeks part of the animals were killed, the morphological changes of liver were observed. The hepatic coefficient were determined after the remaining quails were cholesterol-feeding for 18 weeks. RESULTS Pivanampet alleviated the liver Steatosis induced by cholesterol-feeding in rabbits and quals. It decreased total cholesterol levels, elevated the activity of glutatione peroxidase in the rabbits liver, and reversed the increasing hepatic coefficient in rabbits and quails. CONCLISION The novel compound Pivanampet can delay the formation of fatty liver by cholesterol-feeding.

Due to the completion of human genome project and the advent of new technologies, the traditional drug discovery is shifting to genomics-based drug discovery. Target discovery is an important first step in drug discovery pipeline. In this review, we critically introduce the strategies and biology technologies for target discovery, especially focus on the likely impact of new technologies in drug target research and speculate the future trend of target research.

Objective To observe the effects of 1,3-dipropyl-8-cyclopentylxanthine(DPCPX),an adenosine A1 receptor antagonist,on brain neurons damage induced by hypoxia and reoxygenation(H/R),and to elucidate the relevant mechanisms.Methods An in vitro cultured rat cerebral cortical neuronal H/R damage model was established;the effects of DPCPX were detected at final concentrations of 0(control),25,50,100nmol/L on the lactate dehydrogenase(LDH) release from normoxic neurons and H/R neurons which were treated with hypoxia for 8,12,24 hours followed by reoxygenation for 24 hours;the changes of malondialdehyde(MDA) content,activities of xanthine oxidase(XO) and Ca2+-ATPase in H/R neurons which were treated with hypoxia for 12 hours and reoxygenation for 24 hours brought by administration of DPCPX at the concentration of 100nmol/L were also determined by use of specific reagents.Results With addition of 100nmol/L DPCPX,the LDH release from H/R neurons which were treated with hypoxia for 12 hours and reoxygenation for 24 hours was significantly increased compared with that in control group(P

ATP sensitive potassium channels (K ATP ) have been thought to be a mediator of cardioprotection. Recent pharmacologic and molecular biology studies show the protective effects of K ATP openers are not dependent of action potential shortening and cardiodepressant effects, but mediated by preservation of mitochondrial function, which suggests a role for intracellular mitochondrial K ATP (mito K ATP ). The mechanism by opening mito K ATP produces cardioprotection is less clearer, however, it is thought that a beneficial effect may occur as the result of K + entry and intramitochondrial depolarization. This effect would reduce mitochondrial calcium overload and cause matrix swelling, which are shown to enhance ATP synthesis and stimulate mitochondrial respiration.

AIM To investigate the protective effects of iptakalim hydrochloride (Ipt) against glutamate induced neurotoxity. METHODS Neurotoxity injury was induced by with glutamic acid in PC12 cells. The cell viability was measured by MTT assay. RESULTS Ipt at the concentrations of 1 ? 1(T-10 - 1 ? 1(T4 mol ? L-1 markedly mitigated glutamate-induced neurotoxicity. The protec- live effect was nullified by glibenclamide, an ATP-sensitive potassium channel antagnist. CONCLUSION Ipt provides neuroprotection on glutamate-induced cytotoxixity in cultured PC12 cells and this effect may be related with ATP-sensitive potassium channels.

ATP sensitive potassium channel(K ATP has been indentified in a variety of tissues and recognized as an important drug target.K ATP channels is composed with a 4∶4 stoichiometry of an inwardly rectifying K + channel(Kir) subunit plus a sulfonylurea receptor(SUR).The characteristics for the SUB2B/Kir 6 1 in vascular are small condutance,ATP insensitivity and activation by added NDP.Therefore,it is refered as NDP dependent K + channel(K NDP ).A lot of endogenous and exogenous vasodilators seem to act through a common pathway by opening K ATP in vascular,which is involved in protein kinase A and C signal transduction pathway.Vascular shows different sensitivity to potassium channel openers(KCO),and the mechanism remains to be determined.In this review,a summary of K ATP in vascular is presented with molecular structure,KCO selectivity to tissue,signal pathway,electrophysiological and pharmacological properties.

?7nAChR, an important neurotransmitter recptor,is w il dly expressed in the central and peripheral neuronal system, which is involved i n neuronal signal transduction and the regulation of physiological functions in the central neuronal system. Several studies have demonstrated that ?7nAChR is identified in non-neuronal cells such as endothelial cells, vascular smooth mus cle cells, bronchial epithelial cells, skin keralinocytes and is involved in the regulation of mitosis,differentiation, organization of the cytoskeleton, cell -cell contact, locomotion and migration. These (in vitro and in vivo) s tudies indicated that ?7nAChR participated in the secretion and release of seve ral bioactivity molecules in endothelial cells, mediated intercellular signal tr ansduction, and regulated angiogenesis. These studies suggested an endogenous ch olinergic target for angiogenesis mediated by endothelial ?7nAChR.

Aim To clone the muscarinic receptors M1, M3 and M5 sequences of astrocyte cells,and compare the gene and protein sequences with those of neurons. Methods Specific primers were designed to clone the M1, M3 and M5 sequences of astrocyte cells by RT-PCR according to those of neurons,then sequenced the sequences. Result By comparing the M1, M3 and M5 sequences expression by astrocyte cells with those by neurons and we found four, eight,and one different bases and one, four and one different amino acids in M1, M3 and M5 between astrocyte cells and neurons respectively. Conclusions The gene and protein sequence differences are evident in M1, M3 and M5 between astrocyte cells and neurons.

Aim To investigate the effects of homocysteine on monocyte chemoattractant protein-1(MCP-1),intercellular cell adhesive molecule type-1(ICAM-1),vascular cell adhesive molecule1-1(VCAM-1)mRNA expression and the protective effects of arecoline,PPVP,DMHPPP and simvastatin in cultured bovine aorta endothelial cells,thereby to explore possible mechanisms by which the compounds affect the formation of atherosclerosis(AS).Methods Bovine aorta endothelial cells were cultured in vitro with indicated concentration of HCY for indicated time.After the cells were harvested at the specified situation,the MCP-1,ICAM-1 and VCAM-1 mRNA expression was detected by reverse transcription-polymerase chain reaction(RT-PCR) and normalized to the mRNA level of ?-microglobulin in the absence or in the presence of homocysteine or land arecoline,PPVP,DMHPPP and simvastatin,respectively.Results The expression of MCP-1,ICAM-1 and VCAM-1 mRNA all increased dose-and time-dependently after treatments with 0.1,0.5,5.0 mmol?L~(-1) HCY for 6 h and 0.1 mmol?L~(-1) HCY for 3,6,12,24 h,respectively.Compared with control group,after the bovine aorta endothelial cells were incubated with 10 ?mol?L~(-1) arecoline,PPVP,DMHPPP,simvastatin for 20 h in advance,respectively,the injury effects which were subsequently induced by 0.1 mmol?L~(-1) HCY for 6 h could be prevented.Conclusions Cultured bovine aorta endothelial cells could express MCP-1,ICAM-1,VCAM-1 mRNA at a low level,and HCY could induce a higher expression.The over expression could be blocked by arecoline,PPVP,DMHPPP and simvastatin.