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An increase in opening of BKCa channels in smooth muscle cells in streptozotocin-induced diabetic mice

Acta Pharmacologica Sinica 2004年第6期25卷 42-48页

作者： Chun-ling YE2, Bing SHEN4, Xian-da REN, Rong-jing LUO3, Sheng-yuan DING3, Fu-man YAN3, Jia-hua JIANG department of pharmacology, Pharmacy College of Ji-nan university, Guangzhou 510632 3department of physiology, Guangzhou university of Traditional Chinese Medicine, Guangzhou 510407 4department of Molecular Biology and Cell Biology, School ofLife Sciences, university of Sciences and Technology of China, Hefei 230036, China department of pharmacology Pharmacy College of Ji-nan University Guangzhou 510632 Chin

AIM: To investigate the changes of function of large conductance of calcium-activated potassium channels (BKCa channels) in thoracic aortic smooth muscle cells in early stage of streptozotocin (STZ)-induced diabetic C57BL/6J mice. METHODS: Vascular muscle tension in the isolated thoracic aortic rings of mice was compared, and the role of BKCa channels in relaxation of isolated mice thoracic aortic rings induced by acetylcholine (ACh) was determined. Meanwhile, single vascular smooth muscle cells (VSMCs) were isolated by collagenase, and BKCa currents were recorded by patch-clamp single channel recording technique in symmetric high potassium solution. RESULTS: Tetraethylammonium (TEA) 1 mmol/L, a selective calcium-activated potassium channel blocker, caused significant rightward shift in the concentration-response curves of ACh in the isolated thoracic aortic rings of diabetic mice and pD2 value of ACh-induced relaxation was decreased notably after TEA treatment [(6.3±0.4) vs (6.9±0.5), n=10 rings from 7 mice, P0.05]. Furthermore, conductance of BKCa channels in single thoracic aortic smooth muscle cells was decreased [(199±15) pS, n=10 cells from 7 mice vs (266±11) pS, n=12 cells from 6 mice, P<0.01], but probability of open of BKCachannels was increased [(0.51±0.28) vs (0.11±0.06), n=6 cells from 6 mice, P<0.01], and the mean closed time in diabetic mice was reduced [(15±15) vs (132±98), n=6 cells from 6 mice, P<0.05]. CONCLUSION: The opening of BKCa channels was increased in thoracic aortic smooth muscle cells in the early stage of STZ-induced diabetic C57BL/6J mice by reducing mean closed time, but the conductance of BKCa channels was decreased.

关键词： diabetes mellitus streptozotocin aorta patch-clamp techniques potassium channels calcium

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Minocycline inhibits 5-lipoxygenase activation and brain inflammation after focal cerebral ischemia in rats

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Acta Pharmacologica Sinica 2007年第6期28卷 763-772页

作者： Li-sheng CHU~(2,3),San-hua FANG~2,Yu ZHOU~2,Guo-liang YU~2,Meng-ling WANG~2,Wei-ping ZHANG~2,Er-qing WEI~(2,4)~2 department of pharmacology,School of Medicine,Zhejiang university,Hangzhou 310058,China ~3 department of physiology ZhejiangChinese Medical university Hangzhou 310053,China department of pharmacology School of Medicine Zhejiang University Hangzhou 310058 China

Aim:To determine whether the anti-inflammatory effect of minocycline on postis-chemic brain injury is mediated by the inhibition of 5-lipoxygenase （5-LOX）expression and enzymatic activation in ***:Focal cerebral ischemiawas induced for 30 min with middle cerebral artery occlusion,followed *** ischemic injuries,endogenous IgG exudation,the accumulationof neutrophils and macrophage/microglia,and 5-LOX mRNA expression weredetermined 72 h after reperfusion.5-LOX metabolites （leukotriene B4and cysteinylleukotrienes） were measured 3 h after ***:Minocycline （22.5and 45 mg/kg,ip,for 3 d） attenuated ischemic injuries,IgG exudation,and theaccumulation of neutrophils and macrophage/microglia 72 h after *** inhibited 5-LOX expression 72 h after reperfusion and the production ofleukotrienes 3 h after reperfusion,Conclusion:Minocycline inhibited postis-chemic brain inflammation,which might be partly mediated by the inhibition of5-LOX expression and enzymatic activation.

关键词： minocycline 5-1ipoxygenase leukotriene focal cerebral ischemia inflammation

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INHIBITORY EFFECT OF ELECTRO-ACUPUNCTURE ON cAMP INDUCED ECOG EPILEPTIFORM WAVES

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针刺研究 1989年第Z1期 20-21页

作者： Lou Zhicong department of physiology, The First Military Medical university, Guangzhou

In conscious rabbits, injection of cAMP (100μg in 100μl, icv) elicitedhigh-amplitude and high-frequency epileptiform seizure pattern of ECoG. The(pileptic waves were inhibited by electro-acupuncturing bilateral 'Zus... 详细信息

关键词： cAMP INHIBITORY EFFECT OF ELECTRO-ACUPUNCTURE ON cAMP INDUCED ECOG EPILEPTIFORM WAVES high

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Taurine Inhibits Myocardial Fibrosis via PKC-ERK1/2 Signaling Pathways

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Chemical Research in Chinese Universities 2012年第1期28卷 84-90页

作者： WANG Li-ying1,2, LI Hong1 and YANG Shi-jie1 1. department of pharmacology, Norman Bethune College of Medicine, Jilin university, Changchun 130021, P. R. China 2. department of physiology, Basic Medicine College, Beihua university, Jilin 132013, P. R. China Jilin Univ Norman Bethune Coll Med Dept Pharmacol Changchun 130021 Peoples R China Beihua Univ Basic Med Coll Dept Physiol Jilin 132013 Jilin Peoples R China

Previous studies have demonstrated the important role of taurine in inhibiting proliferation of myofibrob lasts（myoFb） and myocardial fibrosis. However, the underlying mechanisms are unclear. The present study was de signed to shed light on this issue through exploring the signal pathways via in vitro experiments. Angiotension II （AngII） treatment significantly increased myoFb proliferation and the levels of collagens I and III（P〈0.05）, whereas taurine, PKCα（PKC： protein kinase C） specific inhibitor L-threo-dihydro-sphingosine（D4681）, ERK1/2 inhibitor （PD98095） abrogated myoFb proliferation and collagen levels（P〈0.05, P〈0.01, respectively）, and increased the G0/G1 phase rate and decreased S phase rate. Immunocytochemistry, confocal fluorescence staining and image analy sis showed that taurine could inhibit the translocation and expression of p-PKCαin membrane, and then inhibit nuc lear translocation and expression of p-ERK1/2. These results have statistically significant differences compared with those of AngII group（P〈0.01）. Western blot results also show that taurine could inhibit the protein expression of p-PKCα and p-ERK1/2. We used p-PKCα specific inhibitor D4681 in order to elucidate the relationship between p-PKCα and p-ERK1/2 in signal transduction pathways. Finally, the results show that the protein expression of p-ERK1/2 and nuclear translocation were suppressed in D4681 group.

关键词： Taurine Myocardial fibrosis Proliferation Signal transduction Cardiac remodeling

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Surface electrocardiogram and action potential in mice lacking urea transporter UT-B

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Science China(Life Sciences) 2009年第5期52卷 474-478页

作者： MENG Yan1, ZHAO ChunYan2, ZHANG XueXin2, ZHAO HuaShan1, GUO LiRong1, Lü Bin1, ZHAO XueJian1& YANG BaoXue1,3 1 department of Pathophysiology, School of Basic Medicine, Jilin university, Changchun 130021, China 2 department of physiology, School of Basic Medicine, Jilin university, Changchun 130021, China 3 department of Medicine, university of California, San Francisco CA 94143, usa department of Pathophysiology School of Basic Medicine Jilin University Changchun 130021 China department of physiology School of Basic Medicine Jilin University Changchun 130021 China department of Medicine University of California San Francisco CA 94143 USA

UT-B is a urea transporter protein expressed in the kidney and in many non-renal tissues including erythrocytes, brain, heart, bladder and the testis. The objective of this study was to determine the phenotype of UT-B deletion in the heart. UT-B expression in the heart was studied in wild-type mice vs UT-B null mice by utilizing RT-PCR and Western blot. A surface electrocardiogram (ECG) recording (lead II) was measured in wild-type mice and UT-B null mice at the ages of 6, 16 and 52 weeks. For the action potential recording, the ventricular myocytes of 16 w mice were isolated and recorded by floating microelectrode method. The sodium current was recorded by the patch clamp technique. RT-PCR and Western blot showed the UT-B expression in the heart of wild-type mice. No UT-B transcript and protein was found in UT-B null mice. The ECG recording showed that the P-R interval was significantly prolonged in UT-B null mice ((43.5 ± 4.2), (45.5 ± 6.9) and (43.8 ± 7.6) ms at ages of 6, 16 and 52 weeks) vs wild-type mice ((38.6 ± 2.9), (38.7 ± 5.6) and (38.2 ± 7.3) ms, P<0.05). The atrial ventricular heart block type II and III only appeared in the aging UT-B null mice (52 w old). The amplitude of action potential and Vmax decreased significantly in UT-B null mice ((92.17 ± 10.56) and (101.89 ± 9.54) mV/s) vs those in wild-type mice (vs (110.51 ± 10.38) and (109.53 ± 10.64) mV/s, P<0.05). The action potential duration at 50% and 90% (APD50 and APD90) was significantly prolonged in UT-B null mice ((123.83 ± 11.17) and (195.43 ± 16.41) ms) vs that in wild-type mice ((108.27 ± 10.85) and (171.00 ± 15.53) ms, P<0.05). The maximal sodium current decreased significantly in UT-B null mice (-8.80 ± 0.92) nA vs that in wild-type mice ((-5.98 ± 1.07) nA, P<0.05). These results provide the first evidence that UT-B deletion causes progressive heart block in mice.

关键词： urea transporter heart block electrocardiogram

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INVOLVEMENT OF ARCUATE NUCLEUS OF HYPOTHALAMUS IN THE ASCENDING PATHWAY FROM PERIAQUEDUCTAL GREY TO NUCLEUS ACCUMBENS SUBSERVING ANTINOCICEPTIVE EFFECT

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针刺研究 1989年第Z1期 69-70页

作者： Yu Longchuan Han Jisheng department of physiology, Beijing Medical university

It was found that the analgesic effect of morphine administered to peri- aqueductal grcy(PAG) of the rabbit was significantly attenuated by β-EP IgGinjected into the nucleus accumbens. This antagonistic effect was totallyabolished by lesioning of the ARH. However, lesioning of ARH showed nosignificant influence on the analgesia produced by intra-PAG-administeredmorphine, nor did it abolish the reversal of morphine analgesia by naloxoneadministered to nucleus accumbens.

关键词： PAG INVOLVEMENT OF ARCUATE NUCLEUS OF HYPOTHALAMUS IN THE ASCENDING PATHWAY FROM PERIAQUEDUCTAL GREY TO NUCLEUS ACCUMBENS SUBSERVING ANTINOCICEPTIVE EFFECT

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Pharmacokinetics of traditional Chinese syndrome and recipe:a hypothesis and its verification(Ⅰ)

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World Journal of gastroenterology 2000年第3期6卷 384-391页

作者： Xi Huang Ping Ren Ai Dong Wen Li Li Wang Li Zhang Feng gao Laboratory of Clinical pharmacology of Chinese Medicine,Xijing Hospital,The Fourth Military Medical university,Xi’an 710032,Shaanxi Province,China department of Pharmacy,Xijing Hospital,The Fourth Military Medical university,Xi’an 710032,Shaanxi Province,China department of physiology,The Fourth Military Medical university,Xi’an 710032,Shaanxi Province,China 第四军医大学陕西西安

AIM To propose a hypothesis defining theabsorption,distribution,metabolism andelimination of traditional Chinese recipe（TCR）-component in blood of healthy subjects andpatients,and estimate its *** The pharmacokinetics（PK）of samedose of drug was studied in the animal model oftraditional Chinese syndrome（S）and *** classification,terminology,concept and significance of the hypothesis wereset forth with evidence provided in the *** hypotheses consisted of traditionalChinese syndrome PK（S-PK）and traditionalChinese recipe PK（R-PK）.Firstly,the observedtetramethylpyrazine（TMP）PK in healthy,chronically reserpinized rats（rat model ofspleen deficiency syndrome,RMSDS）andRMSDS treated with Sijunzi decoction（SJZD）forconfirmation were used to verify S-PK; secondly,the ferulic acid（FA）PK in healthy andhigh molecular weight dextran（HMWD）-inducedrabbit model with blood stasis syndrome（RDBSS）was also used to verify S-PK;andlastly,TMP PK parameters in serum of healthyrats after orally taken Ligusticum wallichii（LW）,LW and Salvia miltiorrhiza（LW&SM）decoctions were compared to verify *** The apparent first-order absorption[Ka,（13.61±2.56）h-1,area under the blooddrug concentration-time curve[AUC,（24.88±9.76）μg.h-1mL-1],maximum drug concentration[Cmax,（4.82±1.23）μg·mL-1]of serum TMP inRMSDS were increased markedly（P-1,AUC=（5.20±2.57）μg·h-1·mL-1,Cmax=（2.33±1.77）μg·mL-1]of healthy rats（HR）.Theapparent first-order rate constant for α and βdistribution phase[α=（0.38±0.09）h-1,β=（0.06±0.03）h-1,the apparent first-orderintercompartmental transfer rate constants[K10=（0.24±0.07）h-1,K12=（0.11±0.02）h-1,K21=（0.11±0.02）h-1]of serum TMP in RMSDS weredecreased significantly（P10

关键词： traditional Chinese syndrome/recipe Chinese medicine pharmacokinetics blood stasis spleen deficiency hypothesis

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EFFECT OF ENTOPEDUNCULAR NUCLEUS ON THE ANALGESIA IN RAT

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针刺研究 1989年第Z1期 74-75页

作者： Zhang Wei Wang Shao department of physiology, Bethune university of Medical sciences

The aim of this experiment was to clarify if the entopeduncular nucleuscan modulate the pain threshold through habenular nucleus mediated the actionbetween nuclei entopeduncular and habenular. L-glutamic acid (excitatory acid thai can excite the neuron body ratherthan passed fibers), bicuculline (a gaBA receptor antagonist), lidocaine andgaBA were injected into entopeduncular and habenular nuclei respectivelythrough the implanted cannula. Pain threshold was measured by the latencyof avoidance response (tail-flick) elicited by radiant heat applied to the tailskin of animals before and after intracerebral injection. In some cases single-unit activity in the habenular nucleus was recorded when the entopeduncularnucleus was electrically stimulated.

关键词： gaBA EFFECT OF ENTOPEDUNCULAR NUCLEUS ON THE ANALGESIA IN RAT

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p38 MAPK mediates cardiovascular and behavioral responses induced by central IL-1β and footshock in conscious rats

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Acta Pharmacologica Sinica 2004年第3期25卷 12-16页

作者： Rui-mao ZHENG,Chang-jiang ZOU,Shi-gong ZHU2 department of physiology and Pathophysiology,Health Science Center,Peking university,Beijing 100083,China department of physiology and Pathophysiology Health Science Center Peking University Beijing 100083 China

AIM: To investigate the roles of p38 mitogen-activated protein kinase (p38 MAPK) in the cardiovascular and behavioral responses induced by intracerebral ventricular injection (icv) of interleukin-1β (IL-1β) or footshock. METHODS: We examined the effects of p38 MAPK on mean artery blood pressure (mABP), heart rate (HR), and motor activity (MA) during central administration of IL-1β, or footshock after icv SB203580 (a specific inhibitor of the p38 MAPK) with Cardiovascular and Behavior Telemetry System in conscious SD rats. RESULTS: (1) IL-1β (icv) or footshock remarkably rise the mABP, and the maximal changes are (7.8±1.8) and (12.3±3.5) mmHg, respectively, which was abrogated by the pretreatment with p38 inhibitor SB203580 intracerebroventricularly. (2) Compared with icv saline group, the motor activity was significantly decreased in SB203580 group with maximal changes (-7.6±1.1) counts/min after footshock. CONCLUSION: p38 MAPK plays an important role in the pres- sor response induced by central administration of IL-1β or footshock and change of motor activity after footshock in conscious rats.

关键词： mitogen-activated protein kinase p38 interleukin-1 blood pressure motor activity

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AN OBSERVATION OF THE EFFECTS OF ELECTRO-ACUPUNCTURE ON ANTRAL ELECTRIC ACTIVITY IN CONSCIOUS RABBIT AND ELECTRO-ACUPUN-CTURE ON THE RESTORATION OF THIS ELECTRIC ACTIVITY IN DRUG ANAESTHELIZED ANIMAL

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针刺研究 1989年第Z1期 123-124页

作者： Chen Yongyue Huang Zhongsun department of physiology, Chongqing university of Medical Sciences

The present paper used two kinds of antral electril activity: burst of spikesand slow wave, as indicator of antrsl mechanical contraction studied the effectof electro-acupuncture Zusanli point on the movement function of stomach inrabbit. (1) In conscious rabbit, electro-acupuncture "Zusanli" point coulddecrease both the frequency of the burst activity and the amplitude of slowwave as in their higher level, and increase them when they are in lower level,

关键词： AN OBSERVATION OF THE EFFECTS OF ELECTRO-ACUPUNCTURE ON ANTRAL ELECTRIC ACTIVITY IN CONSCIOUS RABBIT AND ELECTRO-ACUPUN-CTURE ON THE RESTORATION OF THIS ELECTRIC ACTIVITY IN DRUG ANAESTHELIZED ANIMAL

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