Zhongguo yao li xue bao = Acta pharmacologica Sinica最新文献

Aim: To study the effects of estradiol (Est) on inward rectifier K+ (IK1) and delayed rectifier K+ (IK) channels in isolated guinea pig ventricular myocytes.

Methods: Using whole cell patch-clamp recording techniques.

Results: Est 10 mumol.L-1 and 100 mumol.L-1 decreased the action potential duration, APD50, from (474 +/- 71) ms to (330 +/- 75) ms and (229 +/- 67) ms (n = 7 cells of 7 guinea pigs, P < 0.05), respectively. Est 100 mumol.L-1 also decreased APD90 from (587 +/- 60) ms to (418 +/- 79) ms (n = 7, P < 0.05). Est inhibited IK tail current (IK.tail) concentration-dependently. IK.tail was depressed 53% (n = 5, P < 0.05) at 10 mumol.L-1 and 80% (n = 5, P < 0.01) at 100 mumol.L-1 compared with control. Est > or = 10 mumol.L-1 blocked IK1. The maximal inhibition of inward current of IK1 occurred at -100 mV test potential was 49% (n = 5, P < 0.01) and outward current of IK1 at -40 mV was 72% (n = 5, P < 0.01). The reverse potential shifted negatively, from -70 to -76 mV.

Conclusion: Est possessed blocking effects on both IK1 and IK channels in guinea pig ventricular myocytes.

Metabotropic glutamate receptors (mGluR) are densely expressed by striatal medium spiny neurons. Activation of mGluR in this brain region alters local transmitter release and behaviors of experimental animals. In particular, mGluR regulate transcription factor and neuropeptide gene expression in striatal neurons through their connections with multiple intracellular effectors. This prominent involvement of mGluR in overall cellular activity is pivotal for the development of neuronal plasticity underlying long-term adaptive changes in cellular physiology related to a variety of neurologic disorders. Accumulating evidence demonstrates that the subtypes of mGluR have distinct effects on gene expression: group I subtypes facilitating, and group II/III subtypes inhibiting, gene expression. Thus, the mGluR can be considered as promising targets in the development of novel therapeutic drugs that can relieve neurologic disorders resulting from dysfunction of the striatum.

Aim: To study the correlation between CYP2D6 genotype and its phenotype.

Methods: CYP2D6 genotyping was made by detecting CYP2D6*3, *4, *6, and *7 alleles with an allele-specific polymerase chain reaction procedure.

Results: The CYP2D6 genotypes were well correlated with its phenotypes in all 125 extensive metabolizers and in 43 poor metabolizers. Extensive metabolizers had at least one wildtype CYP2D6 gene and the genotypes were *1/*1, *1/*3, and *1/*4. Poor metabolizers were found to be homozygous mutants of CYP2D6 gene and the genotypes were *3/*4, *4/*4, *3/*6, *4/*7, *4/*6, and *6/*6.

Conclusion: Genotype could be used to screen variations of CYP2D6 expression.

Aim: To study the effect of tenuifolic saponin (TS) on arterial pressure.

Methods: Mean arterial pressure (MAP) was recorded from left carotid artery in rat which was anesthetized with urethane and then injected i.v. gtt with a transfusion of NaCl 0.15 mol.L-1. Systolic blood pressure (SBP) of conscious rat and renovascular hypertensive rat (RVHR) was measured by tail cuff method.

Results: TS 2, 4, 8 mg.kg-1 i.v., 20 and 40 mg.kg-1 i.g. reduced the MAP by 31%, 37%, 50%, 21%, and 31%, respectively. Bilateral vagotomy plus atropine (Atr) i.v., or pretreatment with diphenhydramine hydrochloride (Dip) failed to influence TS effect. Lack of effect of TS on carotid-occlusion-induced- or epinephrine (Epi)-induced-hypertensive response was found. SBP in conscious rat and RVHR was suppressed, highest by 38.0% and 26.8% at 60 and 90 min, maintaining at least 2 and 3 h, respectively, after i.g. TS 40 mg.kg-1.

Conclusion: TS reduced the arterial pressure, not related to vagus excitation, ganglionic blockade, and peripheral alpha-adrenergic-, M-cholinergic-, and H1-receptors.

Aim: To observe attenuative effects of agmatine on opiate desensitization and substance dependence.

Methods: Guanosine 5'-O-(3-[35S] thiotriphosphate) ([35S]GTTP) binding and cellular cyclic AMP (cAMP) level were determined by radioligand binding assay and radioimmunoassay in NG108-15 cells, respectively.

Results: Agmatine increased stimulative action of opioids on [35S]GTTP binding by about 35% and inhibitory effects of opioids on cellular cAMP concentration by about 114.3% in NG108-15 cells pretreated with opioids. On the other hand, it also inhibited cAMP over-shooting by 214.9% of morphine substance dependent cells precipitated by naloxone compared with that of control. These effects of agmatine were antagonized by idazoxan in a concentration-dependent manner.

Conclusion: Agmatine reversed the formative process of adaptation in cAMP signal transduction cascade.

Aim: To investigate the influence of Ginkgo biloba extract (GbE) on cardiomyocytes damaged by H2O2.

Methods: Cultured rat cardiomyocytes were divided into 3 groups randomly: control group; H2O2 (2.5 mmol.L-1) group; H2O2 2.5 mmol.L-1 + GbE 150 mg.L-1 group. The cardiomyocytes were cultured in MEM (Eagle's) at 37 degrees C in the presence of 5% CO2 for 4 h. Lactate dehydrogenase (LDH) was assayed by colorimetric method. Lipid peroxidation was determined by measuring thiobarbituric acid-reactive substances. Ultrastructure was viewed under transmission electron microscope.

Results: Compared with the control group, LDH leakage and malondialdehyde (MDA) content increased in H2O2 group, LDH increased from (2166 +/- 247) U.L-1 to (5180 +/- 648) U.L-1, MDA increased from (3.5 +/- 0.2) nmol/10(6) cells to (7.2 +/- 0.4) nmol/10(6) cells (P < 0.01). The ultrastructure was damaged seriously. GbE inhibited the increase of LDH leakage and MDA content induced by H2O2. In this group, LDH decreased from (5180 +/- 648) U.L-1 to (3496 +/- 386) U.L-1, MDA decreased from (7.2 +/- 0.4) nmol/10(6) cells to (4.8 +/- 0.9) nmol/10(6) cells (P < 0.01). Ultrastructure of cells was also protected by GbE.

Conclusion: GbE protected the cardiomyocyte against H2O2 injury, the protective action was attributed to its antiperoxidative effect.

Aim: To study the changes of monoamines in ventrolatoral periaqueductal gray of rat brain before and after electroacupuncture (EA) analgesia (EAA) was enhanced by fenfluramine (Fen), a 5-hydroxytryptamine (5-HT) releaser.

Methods: Monoamines were collected by in vivo microdialysis and measured by HPLC connected with electrochemical detector.

Results: The level of norepinephrine (Nor) after EA was decreased (P < 0.05 vs NS group). The contents of 5-HT, 5-hydroxyindol acetic acid (5-HIAA), dopamine (DA), and homovanillic acid (HVA) in periaqueductal gray dialysate were increased (P < 0.05 vs NS group). When Fen was combined with EA, the level of 5-HT and 5-HIAA were further increased (P < 0.05 vs NS + EA group). There was no obvious change of Nor, DA, and HVA.

Conclusion: Fen potentiating EAA may be related to further activation of serotoninergic system.

Aim: To study the efficacy of huperzine-A capsules (Hup) on memory and learning performance of adolescent students.

Methods: Using double-blind and matched pair method, 34 pairs of junior middle school students complaining of memory inadequacy were divided into two groups by normal psychological health inventory (PHI), similar memory quotient (MQ), same sex and class. The Hup group was administrated orally 2 capsules of Hup (each contains Hup 50 micrograms) b.i.d., and the placebo group was given 2 capsules of placebo (starch and lactose inside) b.i.d. for 4 wk.

Results: At the end of trial, the Hup group's MQ (115 +/- 6) was more than that of the placebo group (104 +/- 9, P < 0.01), and the scores of Chinese language lesson in the Hup group were elevated markedly too.

Conclusion: The Hup capsules enhance the memory and learning performance of adolescent students.

Aim: To investigate the effects of MK-447 on platelet shape change, aggregation, and ATP release by collagen (Col), ADP, and stable analogue of thromboxane A2 (STA2) in rabbits.

Methods: Platelet shape change and aggregation were quantified in light transmission by turbidimetric method and release reaction was assessed by the amount of ATP in platelet-rich plasma (PRP).

Results: (1) MK-447 100-700 mumol.L-1 caused only the shape change, which was not inhibited by indometacin 3 mumol.L-1. Platelet shape changes by Col, ADP, and STA2 were reduced (P < 0.01) after the addition of MK-447. The lag phase was prolonged (P < 0.01) in Col and shortened (P < 0.01) in ADP. (2) MK-447 reduced the aggregation by Col 5 mg.L-1 (P < 0.01), and enhanced that by ADP 0.3-10 mumol.L-1 and STA2 0.1-3 mumol.L-1 (P < 0.01). (3) The release reaction by STA2 1-3 mumol.L-1 was also increased (P < 0.01). The effects of MK-447 on STA2 were not inhibited by S-145.

Conclusion: MK-447 induced the platelet shape change, and showed the dual effects, inhibition or enhancement, on the actions by different aggregating agents.

Aim: To study the mechanism of opioid agonists in regulation of cAMP second messenger system.

Methods: Low-pH treatment was used to deplete the stimulatory G protein (Gs) function. The effects of some opiates on adenylate cyclase were compared between control and low-pH treatment membranes.

Results: In contrast to dehydroetorphine (DHE), etorphine (Eto), morphine (Mor) and methadone (Met) substantially increased the inhibitory effects on adenylate cyclase in membranes prepared from naive and chronic Mor- or Met-treated NG108-15 cells by low-pH treatment. In contrast to Mor, DHE and Eto did not result in significant decrease in the inhibitory effects on adenylate cyclase in membranes from the cells treated chronically with DHE or Eto. Marked rebound of adenylate cyclase was also not observed in membranes from chronic DHE or Eto-treated cells when precipitated with naloxone. Low-pH treatment eliminated naloxone-induced rebound of adenylate cyclase in chronic Mor-treated cells.

Conclusion: The difference in opiate-induced functional adaptive alteration of Gs is at least one biochemical mechanism of developing opiate tolerance and dependence.