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Isoprenaline enhances local Ca2. release in cardiac myocytes

Acta Pharmacologica Sinica 2006年第7期27卷 927-932页

作者： Jian-xin SHEN~(2.3,42.department of physiology,Shantou University medical {2.,Shantou 515041,china 3 department of physiology,medical School of Xi'an Jiaotong University,Xi'an 710061,china department of physiology Shantou University Medical College Shantou China department of physiology Medical School of Xi'an Jiaotong University Xi'an China

Aim:Contraction of cardiac myocytes is controlled by the generation and ampli-fication of intracellular Ca2.*** key step of this process is the couplingbetween sarcolemma L-type Ca2.channels（LCCs）and ryanodine receptors（RyRs）in the sarcoplasmic reticulum（SR）.β-Adrenergic stimulation is an important regu-latory mechanism for this coupling *** the details underlied the globallevel,which require local Ca2.release study are still *** present study isto explore the effects of β-adrenergic stimulation on local Ca2.***:Using confocal microscopy combined with loose-seal patch-clamp approaches,effects of isoprenaline(1 μmol·L-1),a β-adrenergic agonist,on local SR Ca2.re-lease triggered by Ca2.influx through LCCs in intact rat cardiac myocytes ***:Isoprenaline increased the intensity of ensemble averagedlocal Ca2.transients,the peak of which displayed a typical bell-shaped voltage-dependence over the membrane voltages ranging from～-40mV to～+35m ***-ther analysis showed that this enhancement could be explained by the increasedcoupling fidelity（which refers the increased probability of RyRs activation upondepolarization）,and the increased amplitude of evoked Ca2.sparks(due to moreCa2.releases through local RyRs).In addition,isoprenaline decreased the firstlatency,which displayed a typical"U"-shaped voltage-dependence,showing theavailable acceleration and synchronization of β-adrenergic stimulation on intrac-ellular calcium ***:Isoprenaline enhances local Ca2.release incardiac *** results underscore the importance of regulation of β-adrenergic stimulation on local intermolecular signals between LCCs and RyRs inheart cells.

关键词： local calcium release calcium signaling cardiac myocytes isoprenaline confocal microscopy

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Phytoestrogen genistein decreases contractile response of aortic artery in vitro and arterial blood pressure in vivo

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Acta Pharmacologica Sinica 2004年第3期25卷 59-64页

作者： Hong-fang LI1,Long-de WANG2.Song-yi QU department of physiology,Lanzhou {2. college,Lanzhou 730000 2.ffiliated Hospital,Gansu Chinese {2. college,Lanzhou 73002.,china department of physiology Lanzhou Medical College Lanzhou 730000 Affiliated Hospital Gansu Chinese Medical College Lanzhou 730020

AIM: To determine the mechanisms of effects of phytoestrogen genistein on the contracted rabbit aortic arteries in vitro, and observe the effect of genistein and 17-β estradiol on mean arterial pressure (MAP) in ovariectomized (OVX) rats. METHODS: (1) Strips of rabbit aortic smooth muscle were suspended in organ baths containing Kreb’s solution, and then isometric tension was measured. (2. Female mature Wistar rats underwent a bilateral ovariectomy (OVX). Sham-operated rats (SHAM) were used as controls. After administration of genistein (0.4 mg·kg-1·d-1, sc), 17-β estradiol (1 mg·kg-1·d-1, sc) or theirvehicle sesame oil for 2. d,MAP was measured. RESULTS: (1) Similar to 17-β estradiol, genistein could dose-dependently relax 40 mmol/L KCl-precontracted arterial strips. Incubation with Nω-L-nitro-arginine (L-NNA), methylene blue (MB), indomethacin, propranolol or endothelium removal did not affect relaxation induced by genistein. In calcium-free solution containing 0.01mmol/L egtazic acid (EGTA), genistein inhibited not only the first phase contraction induced by noradrenaline (NA), but also the second contraction induced by CaCl2. In addition, genistein could reduce the contractile responses of NA, KCl and CaCl2. and shift their cumulative concentration-response curves rightward. (2. MAP in OVX rats was significantlyhigher compared with that of SHAM rats. However,after chronically treatment with genistein or 17-β estradiol for 2. d the baseline MAP in OVX rats was reduced significantly. CONCLUSIONS: (1) The vasodilator effect of genistein in vitro is endothelium independent and not related to the nitric oxide, its mechanisms being probably due to inhibition of Ca2. influx through calcium channels in a noncompetitive manner and Ca2. release from intracellular store induced by NA. (2. Administration of genistein or 17-β estradiol can chronically decrease MAP in OVX rats.

关键词： genistein aorta smooth muscle muscle relaxation calciumchannel vascular endothelium blood pressure

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Effect of an impurity on 3-electron quantum dots in magnetic fields

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Science china(Physics,Mechanics & Astronomy) 2004年第5期47卷 521-530页

作者： LIU Yimin1,2. HUANG Gangming1 & BAO Chengguang1 1. department of Physics, Zhongshan University, Guangzhou 5102.5, china 2. department of Physics, shaoguan University, shaoguan 512.05, china department of Physics Zhongshan University Guangzhou China department of Physics Shaoguan University Shaoguan China

The ground-state property of a 2.dimensional 3-electron quantum dot (QD) subjected to an external magnetic fieldB and affected by an impurity is studied. The impurity is located at thez-axis by a distanced from the plane of the dot. The evolution of the angular momentumL o and the spinS o of the ground state in accordance withB andd has been calculated, and the results are summarized and plotted in a (L o,S o) diagram. The spatial distribution of the electrons (the size and the geometric features) and the optical absorption have also been investigated. The (L o S o) diagram indicates thatL o andS o may jump whend and/orB vary. It was found that, due to the constraints arising from symmetry, each symmetric geometry is accessible only to a specific group of states having specificL o andS o.

关键词： quantum dot, ground state, charged impurity, magnetic field.

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Autoantibody against Cardiac β1-Adrenoceptor Induces Apoptosis in Cultured Neonatal Rat Cardiomyocytes

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Acta Biochimica et Biophysica Sinica 2006年第7期38卷 443-449页

作者： Yan GAO~1 Hui-Rong LIU~1 Rong-Rui ZHAO~1 Jian-Ming ZHI~(2.) 1 department of Cardiovascular physiology Shanxi {2. University,Taiyuan 030001,china 2.department of physiology,Shanghai Jiaotong University,college of Basic Medicine,Shanghai 2.002.,china department of Cardiovascular physiology Shanxi Medical UniversityTaiyuan 030001 China department of physiology Shanghai Jiaotong University College of Basic MedicineShanghai 200025 China

To clarify whether apoptosis is involved in the injury processes induced by autoantibodyagainst cardiac β1-adrenoceptor,we investigated the biological and apoptotic effects of antibodies on culturedneonatal rat *** rats were immunized with peptides corresponding to the second extra-cellular loop of the β1-adrenoceptor to induce the production of anti-β1-adrenoceptor antibodies in the ***（Ig）G in the sera was detected using synthetic antigen enzyme-linked immunosorbentassay and purified using the diethylaminoethyl cellulose ion exchange *** of cardiomyo-cytes was evaluated using agarose gel electrophoresis and flow *** results showed that thepositive serum IgG greatly increased the beating rates of cardiomyocytes and showed an"agonist-like"***,positive serum IgG induced cardiomyocyte apoptosis after treatment with β1-adrenoceptor overstimulation for *** effects of monoclonal antibody against β-adrenoceptor werealso found to be similar to those of positive serum *** was suggested that the autoantibody could inducecardiomyocyte apoptosis by excessive stimulation of β1-adrenoceptor.

关键词： β1-adrenoceptor rat cardiomyocyte autoantibody apoptosis

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Role of melatonin in Alzheimer-like neurodegeneration

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Acta Pharmacologica Sinica 2006年第1期27卷 41-49页

作者： Jian-zhi WANG~(2.4) Ze-fen WANG~(2.3)2.Pathophysiology department,Key Laboratory of Neurological Diseases of Hubei Province,Tongji {2. School,Huazhong University of Science and Technology,Wuhan 430030,china 3 department of physiology,{2. college,Wuhan University Wuhan 430071,china Pathophysiology department Key Laboratory of Neurological Diseases of Hubei Province Tongji Medical School Huazhong University of Science and Technology Wuhan China department of physiology Medical College Wuhan University Wuhan China

Alzheimer disease (AD),an age-related neurodegenerative disorder with progres-sive loss of memory and deterioration of comprehensive cognition,is character-ized by extracellular senile plaques of aggregated β-amyloid (Aβ),and intracellularneurofibrillary tangles that contain hyperphosphorylated tau *** showed that melatonin,an indoleamine secreted by the pineal gland,mayplay an important role in aging and AD as an antioxidant and *** decreases during aging and patients with AD have a more profoundreduction in this *** from clinical trials indicate that melatonin supple-mentation improves sleep,ameliorates sundowning,and slows down the progres-sion of cognitive impairment in Alzheimer's *** efficiently pro-tects neuronal cells from Aβ-mediated toxicity via antioxidant and anti-amyloidproperties:it not only inhibits Aβ generation,but also arrests the formation ofamyloid fibrils by a structure-dependent interaction with Aβ.Our recent studieshave demonstrated that melatonin efficiently attenuates Alzheimer-like *** the exact mechanism is still not fully understood,a direct regulatory influence of melatonin on the activities of protein kinases andprotein phosphatases is ***,melatonin also plays a role inprotecting cholinergic neurons and in ***,the neuroprotectiveeffects of melatonin and the underlying mechanisms by which it exerts its effectsare *** capacity of melatonin to prevent or ameliorate tau and Aβpathology further enhances its potential in the prevention or treatment of AD.

关键词： Alzheimer disease melatonin tau,beta amyloid

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Estrogen stimulates release of secreted amyloid precursor protein from primary rat cortical neurons via protein kinase C pathway

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Acta Pharmacologica Sinica 2005年第2期26卷 171-176页

作者： Sun ZHANG~2.Ying HUANG~2.Yi-chun ZHU~2.Tai YAO~(2.3,4)~2.0} of physiology and Pathophysiology ~3State Key Laboratory for medical Neurobiology,Shanghai medical college of FudanUniversity,Shanghai 2.0032.china department of physiology and Pathophysiology Shanghai Medical College of Fudan University Shanghai China State Key Laboratory for medical Neurobiology Shanghai Medical College of Fudan University Shanghai China

Aim:To investigate the mechanism of the action of estrogen,which stimulates therelease of secreted amyloid precursor protein α(sAPPα)and decreases the gen-eration of amyloid-β protein(Aβ),a dominant component in senile plaques in thebrains of Alzheimer's disease ***:Experiments were carried out inprimary rat cortical neurons,and Western blot was used to detect sAPPα in aculture medium and the total amount of cellular amyloid precursor protein(APP)***:17β-Estradiol(but not 17α-estradiol)and β-estradiol 6-(O-carboxymethyl)oxime:BSA increased the secretion of sAPPα and this effect wasblocked by protein kinase C(PKC)inhibitor calphostin C,but not by the classicalestrogen receptor antagonist ICI 182.***,17β-estradiol did not alterthe synthesis of cellular ***:The effect of 17β-estradiol on sAPPαsecretion is likely mediated through the membrane binding sites,and needs mo-lecular configuration specificity of the ***,the action of the PKC-dependent pathway might be involved in estrogen-induced sAPPα secretion.

关键词： Alzheimer disease estrogen amyloid precursor protein estrogen receptors protein kinase C

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Anisotropic effect on the vibronic reduction factors

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Chinese Science Bulletin 2006年第21期51卷 2553-2558页

作者： QIU Qing-chun1,2.& QIAO Fen1,2.1. department of Physics and IT, medical {2., Shantou University,Shantou 515041, china 2. department of Physics, Shantou University, Shantou 515063, china department of Physics and IT Medical College Shantou University Shantou China department of Physics Shantou University Shantou China

The reduction factors p and q defined by Ham in the Ee JT system and their relation 2.-p=1 have been well accepted and the concept of reduction factors is widely used in the studies of vibronic coupling. However, when the system is under the anisotropic conditions, the reduction factors and their relation will change accordingly. The first-order reduction factors p and q of Ee system were further studied using the method of unitary transformation here. The relation between p and q proposed by Ham was investigated under both conditions of the linear coupling and the anisotropic effects. The result demonstrated that the relation of 2.-p=1 was only correct for the linear vibronic coupling, but not correct when the anisotropic effect was considered. This result suggested that the anisotropic effect influence considerably the reduction factors, and hence the physical properties of materials. Our method could be also applied to other JT systems, especially the highly symmetric JT systems involving C60 molecules.

关键词：电子振动耦合声子交迭 Jahn-Teller效应各向异性

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Alterations of placental cytochrome P450 1A1 and P-glycoprotein in tobacco-induced intrauterine growth retardation in rats

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Acta Pharmacologica Sinica 2005年第11期26卷 1387-1394页

作者： You-e YAN~2. Hui WANG~(2.3), Ymg-hong FENG~2.~2.department of Pharmacology, medical {2. of Wuhan University, Wuhan 430071, china department of Pharmacology Medical College of Wuhan University Wuhan China

Aim: To investigate the alterations of placental P-glycoprotein (P-gp) and cytochrome P450 1 Al (CYPlAl) at different gestational days (GD), and to explore the possible significance of placental P-gp and CYPlAl in tobacco smoke-induced intrauterine growth retardation (IUGR) in rats. Methods: An IUGR model was produced by passive tobacco smoking from GD 7 to parturition (GD 2.) and predicted using fetal development parameters. Placental structure and function were monitored by observing pathological alteration and antioxidative function, including the content of malondialdehyde and the activities of superoxide dismutase and catalase (CAT). The expressions of CYPlAl and P-gp (mdr la and mdr lb) were detected using a reverse transcription polymerase chain reaction and immunohistochemistry. Results: Placental pathological changes occurred and the malondialdehyde content increased, whereas the activities of superoxide dismutase and CAT lowered, when compared to their controls. In the rat placenta of the tobacco group, the level of CYPlAl mRNA increased significantly; the level of mdr1a mRNA increased significantly at GD 2. but not at GD 14, whereas the level of mdr1b mRNA in different term remained stable; the expression of P-gp increased significantly only in full-term placenta. Conclusion: The expression of placental CYPlAl and P-gp increased in tobacco-induced IUGR. Overexpression of placental CYPlAl can attribute to the metabolism of tobacco and the generation of reactive metabolites, which can trigger IUGR. As a compulsory mechanism, upregulation of P-gp might decrease tobacco exposure to a developing fetus with IUGR

关键词： intrauterine growth retardation tobacco placenta cytochrome P450 1A1 P-glycoprotein rats

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Fuzzy controllers based on some fuzzy implication operators and their response functions

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Progress in Natural Science:Materials International 2004年第1期14卷 16-21页

作者： LI Hongxing 1*, YOU Fei 1 and PENG Jiayin 2.1. department of Mathematics, Beijing Normal University, Beijing 100875, china 2. department of Mathematics, Neijiang Teacher's college, Neijiang 641112. china) Beijing Normal Univ Dept Math Beijing 100875 Peoples R China

The fuzzy controllers constructed by 2. fuzzy implication operators based on CRI algorithm and their response functions are discussed. The conclusions show that the fuzzy controllers constructed by 9 fuzzy implication operators are universal approximators to continuous functions and can be used in practical fuzzy control systems. And these 9 fuzzy implication operators except for Einstein operator intersection are all the adjoint pairs of some fuzzy implication operators. Besides, there are 3 other fuzzy controllers formed by fuzzy implication operators being regarded approximately as fitted functions.

关键词： fuzzy implication operators CRI algorithm fuzzy controllers response functions universal approximators

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Sodium dimercaptopropane sulfonate as antidote against non-metallic pesticides

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Acta Pharmacologica Sinica 2004年第4期25卷 136-146页

作者： Zhi-kang CHEN, Zhong-qiu LU1,2. department of Pharmacology, School of Pharmacy, Wenzhou medical {2., Wenzhou 32.035 2.mergency department, TheFirst Affiliated Hospital of Wenzhou medical {2., Wenzhou 32.000, china department of Pharmacology School of Pharmacy Wenzhou Medical College Wenzhou 325035

Sodium dimercaptopropane sulfonate is used in place of dimercaprol in the treatment of poisoning by heaving metals and metalloids as a well-known specific antidote. It is claimed to be less toxic. In early stage, the pharmacologists and clinical doctors in Wenzhou medical college found this drug as antidote against non-metallic pesticides as nereistoxin insecticides, Chlordimeform, bactercide 402. and tetramine. We did a lot of animal experiments and clinical trials to confirm that this antagonist possesses a strong antidotal effect. Now it is widely used in{2.. Great break through has been made not only in the theory but also in its practice. Furthermore, the combination use of this antidote and central anticonvulsant as diazepam indicated synergistic antidotal effect, which is probably the best utilization in the treatment of acute poisoning by tetramine.

关键词： sodium dimercaptopropane sulfonate antidotes pesticides nereistoxin insecticides chlordimeform bactericide 402 tetramine poisoning

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