Modulation of NMDA receptor by huperzine A in rat cerebral cortex. (49/3151)

AIM: To investigate the effects of huperzine A (Hup A) on NMDA receptors in rat cerebral cortex. METHODS: 1) The effect of hup A on NMDA-induced current was studied in acutely dissociated rat hippocampal pyramidal neurons using whole-cell recording. 2) The effect of Hup A on NMDA receptor binding was assessed using [3H] dizocilpine (Diz) binding assay in synaptic membrane preparation of rat cerebral cortex. RESULTS: 1) Hup A reversibly inhibited NMDA-induced current in a concentration-dependent manner with IC50 of 45.4 mumol.L-1. 2) Hup A inhibited the specific binding of [3H]MK-801 to extensively washed synaptic membrane of rat cerebral cortex in a concentration-dependent manner with IC50 of 0.5 (0.1-1.9) mumol.L-1 (n = 4). 3) L-Glutamate 10 mumol.L-1 markedly increased [3H] MK-801 binding. In the presence of L-glutamate, Hup A 0.001-0.1 mumol.L-1 caused a further increase of the binding, whereas Hup A 1-300 mumol.L-1 inhibited the binding in a concentration-dependent manner with IC50 of 12.3 (5.8-26.3) mumol.L-1 (n = 5). CONCLUSION: Hup A acted as an antagonist of NMDA receptor in cerebral cortex in addition to its inhibitory effect on acetylcholinesterase.  (+info)

Synergistic anticancer effects of tetrandrine combined with doxorubicin or vincristine in vitro. (50/3151)

AIM: To study the interaction between tetrandrine (Tet) and doxorubicin (Dox) or vincristine (Vin) against human breast cancer cell lines MCF-7 and MCF-7/Dox or human nasopharyngeal cancer cell lines KB and KBV200 in vitro. METHODS: Anticancer activities of a drug alone and a drug combination of Tet and Dox or Vin were determined by tetrazolium (MTT) method. The interaction between Tet and Dox or Vin was evaluated by both a value of a sum of fractional inhibitory concentration (SFIC) and an isobologram method. RESULTS: The SFIC values of the three-different-ratio combinations between Tet and Dox ranged from 0.14 to 0.38 for MCF-7, and 0.10 to 0.29 for MCF-7/Dox; those of Tet-Vin combinations ranged from 0.21 to 0.37 for KB, and 0.32 to 0.63 for KBV200. All the SFIC values of the combination between Tet and Dox or Vin were less than 1.0 when the 3 ratios of the 2 drugs in combination were used, and the shapes of isobolic curves obtained from the combination were concave. CONCLUSION: The interaction between Tet and Dox or Vin against the human cancer cells was markedly synergistic.  (+info)

Inhibitory effects of huperzine B on cholinesterase activity in mice. (51/3151)

AIM: To determine the anticholinesterase properties of huperzine B (Hup B) and compare with tacrine in vitro and in vivo. METHODS: Spectrophotometry was used to determine ChE activity. RESULTS: Hup B showed much more selective inhibition to acetylcholinesterase (AChE) than tacrine. The IC50 ratios of Hup B and tacrine for butyrylcholinesterase (BuChE): AChE were 65.8 and 0.54, respectively. Hup B ig exhibited higher efficacy on the inhibition of brain AChE than that of tacrine. Tacrine was more effective in the inhibition of serum BuChE in mice with severe concomitant peripheral adverse effects than Hup B. A single ig dose of Hup B produced steady state of AChE inhibition in 4 h. CONCLUSION: Hup B exhibits higher selectivity and efficacy in the inhibition of AChE, and lower toxicity in mice than tacrine.  (+info)

Dual effects of tetrandrine on calcium-activated potassium channels in pulmonary artery smooth muscle cells. (52/3151)

AIM: To study the effects of tetrandrine (Tet) on calcium-activated potassium channels. METHODS: Inside-out configuration of patch-clamp single channel recording techniques. RESULTS: Tet 7.5 and 15 mumol.L-1 increased the open probability from control value 0.251 +/- 0.012 to 0.340 +/- 0.013 and 0.415 +/- 0.011, respectively (P < 0.01), decreased the close time from (61 +/- 15) ms to (33 +/- 10) and (28 +/- 11) ms, respectively (P < 0.01). But Tet 30 mumol.L-1 decreased the open probability and open time to (0.114 +/- 0.008) and (1.47 +/- 0.09) ms, respectively [P < 0.01 vs control (0.251 +/- 0.012) and (20 +/- 8) ms]. CONCLUSION: Tet has concentration-dependent dual effects on KCa channels in isolated rat pulmonary smooth muscle cells.  (+info)

Securinine induced apoptosis in human leukemia HL-60 cells. (53/3151)

AIM: To study whether securinine might induce apoptosis in human leukemia HL-60 cells. METHODS: Inhibition of proliferation was measured using MTT assay. The amount of apoptotic cells was measured by flow cytometry. DNA fragmentation was visualized by DNA agarose gel electrophoresis and the cellular changes were observed by electron microscope. RESULTS: Securinine 5-80 mg.L-1 elicited typical apoptosis morphological changes and DNA fragmentation in a concentration-dependent manner in HL-60 cells. Securinine inhibited HL-60 cell proliferation in a time- and concentration-dependent manner. The IC50 and 95% confidence limits were 27 (15-47) mg.L-1 after 12-h treatment with securinine. CONCLUSION: Securinine induced apoptosis in HL-60 cells.  (+info)

Antagonistic effects of berbamine on [Ca2+]i mobilization by KCl, norepinephrine, and caffeine in newborn rat cardiomyocytes. (54/3151)

AIM: To study the effects of berbamine (Ber) on intracellular calcium concentration ([Ca2+]i) mobilized by KCl depolarization, norepinephrine (NE), and caffeine. METHODS: [Ca2+]i was measured with fluorescent intensity (FI) by confocal microscope in single cultured cardiomyocytes of newborn rats loaded with Fluo 3-AM 2 mumol.L-1. RESULTS: FI value of [Ca2+]i in control level was 248 +/- 70 in the presence of extracellular calcium 1.5 mmol.L-1 and was not changed by Ber 3-30 mumol.L-1. KCl (60 mmol.L-1)- and NE (30 mumol.L-1)-induced [Ca2+]i mobilizations were inhibited (P < 0.01) by Ber 30 mumol.L-1, similar to that of verapamil (Ver). The inhibitory effect of Ber on [Ca2+]i induced by KCl was further increased (P < 0.05) in the presence of egtazic acid 3 mmol.L-1, but that on [Ca2+]i induced by NE was not changed. The [Ca2+]i mobilized by caffeine 80 and 160 mumol.L-1 in D-Hanks' solution was not affected (P > 0.05) by Ber and Ver. CONCLUSION: Ber possessed the antagonistic effects on [Ca2+]i increases via voltage-dependent Ca2+ channel and receptor-operated Ca2+ channel in newborn rat cardiomyocytes, but without effect on intracellular Ca2+ release.  (+info)

Effect of protopine on cytosolic Ca2+ in rabbit platelets. (55/3151)

AIM: To study the influence of protopine (Pro) on the cytoplasmic free Ca2+ concentration ([Ca2+]i) in rabbit platelets. METHODS: Measurement of [Ca2+]i of platelets in vitro by Fura 2-AM fluorescence technique. RESULTS: In the presence of CaCl2 1 mmol.L-1, Pro 10, 20, and 40 mumol.L-1 attenuated the rise in [Ca2+]i evoked by ADP from (420 +/- 57) to (320 +/- 26), (264 +/- 21), and (180 +/- 14) nmol.L-1, respectively, by arachidonic acid (AA) from (280 +/- 36) to (210 +/- 17), (184 +/- 21), and (143 +/- 16) nmol.L-1, respectively, and by platelet-activating factor (PAF) from (350 +/- 42) to (282 +/- 31), (223 +/- 30), and (165 +/- 15) nmol.L-1, respectively. In the presence of egtazic acid 1 mmol.L-1, Pro 10, 20, and 40 mumol.L-1 reduced the Ca2+ release induced by ADP, AA, and PAF, respectively. Pro 10, 20, and 40 mumol.L-1 also decreased ADP-, AA-, and PAF-induced Ca2+ influx. CONCLUSION: Pro inhibited not only Ca2+ release but also the influx of Ca2+.  (+info)

Atriopeptin, sodium azide and cyclic GMP reduce secretion of aqueous humour and inhibit intracellular calcium release in bovine cultured ciliary epithelium. (56/3151)

This study examined the involvement of cyclic GMP, protein kinase G and intracellular Ca2+ movements in the modulation of aqueous humour formation. Using the bovine arterially-perfused eye preparation, drug effects on intraocular pressure and aqueous humour formation rate were measured by manometry and fluorescein dilution, respectively. Drug effects on intracellular [Ca2+] were determined by fura-2 fluorescence ratio technique in nontransformed, cultured ciliary epithelium. Intra-arterial injection of atriopeptin (50 pmol) or sodium azide (10 nmol) produced significant reduction in aqueous humour formation (>38%). This was blocked by selective inhibition (KT-5823) of protein kinase G, but not by selective inhibition (KT-5720) of protein kinase A. Reductions of intraocular pressure produced by atriopeptin or azide were almost completely blocked by KT-5823. ATP (100 microM) caused rapid, transient increase in intracellular Ca2+ followed by a slow decline and prolonged plateau. This response showed concentration-dependent inhibition by atriopeptin, azide or 8-bromo cyclic GMP, and this inhibition of the rapid (peak) Ca2+ increase was enhanced by zaprinast (100 microM; phosphodiesterase inhibitor). KT-5823 blocked the suppression of the peak Ca2+ response but not suppression of the plateau. Arterial perfusion of ATP (0.1-100 microM) produced a concentration-dependent decrease in aqueous humour formation. Aqueous humour formation in the bovine eye can be manipulated through cyclic GMP, operating via protein kinase G. Close parallels appear when Ca2+ movements are modified by similar manipulations of cyclic GMP, suggesting that Ca2+ transients may play an important role in aqueous humour formation and that interplay occurs between cyclic GMP and Ca2+.  (+info)