Inhibitory effects of tetrandrine on Bay k 8644-stimulated contraction of isolated rabbit aortic strips.
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In the presence of KCl 19 mmol.L-1, calcium agonist Bay k 8644 0.47 mumol.L-1 elicited a strong contraction of isolated rabbit aortic strips, and this contraction was concentration-dependently inhibited by tetrandrine; but this antagonism was noncompetitive. Calcium ionophore calcimycin evoked contraction was markedly depressed by tetrandrine. The results suggested that tetrandrine might not only inhibit transmembrane influx of calcium via potential-dependent channels but also interfere with other processes related to calcium. (+info)
Direct radical scavenging by the bisbenzylisoquinoline alkaloid cepharanthine.
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Cepharanthine (Ceph) is known as a potent antiperoxidative agent. Recently, we characterized the antiperoxidative effects of Ceph [Biochim. Biophys. Acta 1426 (1999) 133]. However, it was not clear whether the antiperoxidative effect is really due to its direct radical scavenging activity. Therefore, we studied the interaction of Ceph with the hydroxyl radical (*OH) by the electron paramagnetic resonance (EPR) technique. Results showed that Ceph actually scavenged *OH derived by the Fenton reaction. We also found that Ceph radicals were generated on interaction of Ceph with *OH in neutral aqueous solution, but not in acidic solution, consistent with the pH-dependent anti-lipid peroxidation activity of Ceph. Hence, we concluded that anti-lipid peroxidation by Ceph is due to its direct radical scavenging activity. (+info)
Inhibition of neutrophil priming and tyrosyl phosphorylation by cepharanthine, a nonsteroidal antiinflammatory drug.
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Receptor-mediated superoxide (O2.-)-generation and tyrosyl phosphorylation of neutrophil proteins, such as 58, 65, 84, 108 and 115 kDa, were enhanced by priming cells with granulocyte colony stimulating factor (G-CSF) [Akimura, K. et al. Arch. Biochem. Biophys. 298: 703-709, 1992]. To elucidate the possible involvement of tyrosyl phosphorylation of neutrophil proteins in the enhancing mechanism of O2.- generation, the effect of cepharanthine, a biscoclaurine alkaloid that inhibits phorbol 12-myristate 13-acetate (PMA)- and receptor-mediated O2.- generation, on the priming of human peripheral neutrophils (HPPMN) was studied. Both enhancement of formyl-methionyl-leucyl- phenylalanine (FMLP)-mediated O2.- generation and tyrosyl phosphorylation of some neutrophil proteins, i.e., 115, 108 and 84 kDa proteins, by HHPMN after treatment with G-CSF were strongly inhibited by cepharanthine in a concentration- and treatment-time-dependent manner. In contrast, inhibition of PMA-mediated O2.- generation by cepharanthine was weak and independent of treatment time. These results suggest that cepharanthine might inhibit the priming step of neutrophil activation concomitantly with its inhibition of the tyrosyl phosphorylation of some neutrophil proteins that might underlie the mechanism for priming of neutrophils with G-CSF. (+info)
Tetrandrine is not a selective calcium channel blocker in vascular smooth muscle.
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The effects of tetrandrine (Tet) on the contractile properties of rat aortic ring preparations were studied to test the hypothesis that Tet is a Ca2+ antagonist acting on voltage-operated Ca2+ channels (VOC). The tests were performed on contractions induced by depolarizing concentrations of KCl and by alpha 1-adrenoceptor agonist, phenylephrine (Phe). These vascular effects of Tet were compared to those of nifedipine (Nif). We found that Tet behaved qualitatively similar to, but less potent than, Nif in that it inhibited KCl-induced contraction in a concentration-dependent fashion and its inhibitory effect was long-lasting. However, the effects on Phe-induced contraction of Tet was different from those of Nif in that the extracellular Ca(2+)-dependent contraction was inhibited by Tet, but not by Nif. Tet (60 mumol.L-1) completely inhibited the 45Ca2+ uptake induced by KCl and Phe in rat aortic muscle strips. When the aortic muscle contractile response was induced by addition of Ca2+ following depletion of intracellular stores by Phe in the presence of sarcoplasmic reticulum Ca(2+)-pump inhibitor, cyclopiazonic acid, Tet (60 mumol.L-1) was more effective than Nif 1 mumol.L-1 in inhibiting such a response to extracellularly added Ca2+. Furthermore, Tet, but not Nif, also significantly inhibited the contraction to Phe in Ca(2+)-free medium. Collectively, these results led us to conclude that Tet does not behave as a selective VOC blocker like Nif. (+info)
Frequency-dependent depression of Vmax in K(+)-depolarized guinea pig papillary muscle by tetrandrine.
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The effect of tetrandrine (Tet), a calcium antagonist, on the maximal upstroke velocity (Vmax) of depolarization in K(+)-depolarized guinea pig papillary muscles was studied by standard microelectrode method with computer. The results showed that: (1) the resting block of Tet on Vmax was concentration dependent; (2) the drug (50 or 100 mumol.L-1) caused a marked frequency-dependent block of Vmax, which accounted for 65 +/- 8% of total block at a concentration of 100 mumol.L-1 and the pacing frequency of 0.3 Hz; (3) the recovery kinetics of Vmax could be characterized as a biexponential function, of which the second phase was prolonged by the drug; (4) compared with verapamil, nitrendipine, and diltiazem, the above-mentioned effects of Tet on Vmax were similar to those of diltiazem. These results suggest that Tet can block calcium channel in both frequency-dependent and frequency-independent manner, mainly the former. (+info)
Effects of berbamine on contraction and Ca2+ influx of pig basilar artery.
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Effects of berbamine (Ber) on KCl- and 5-HT-induced contraction of basilar artery (BA) of pigs were studied in vitro. Ber relaxed markedly KCl-induced contraction of BA (IC50 = 4.63 mumol.L-1) and its effect was antagonized by increasing the concentration of extracellular Ca2+; Ber inhibited 5-HT-induced contraction of BA, showing significant inhibition of sustained tonic contraction (STC) (IC50 = 0.64 mumol.L-1) whereas the initial fast phasic contraction (FPC) was relatively unaffected (IC50 = 19.8 mumol.L-1); the 5-HT-induced contraction of BA was dependent on the concentration of extracellular Ca2+, especially STC. The results of Ca2+ withdrawal and replacement indicated that STC was due to 5-HT-stimulated Ca2+ influx, while 5-HT-induced release of intracellular Ca2+ resulted in FPC. Ber 0.8 mumol.L-1 produced markedly inhibitory effect on Ca2+ influx induced by 5-HT (P < 0.01). The effects of Ber were similar to those of nimodipine (Nim). The present results suggested that Ber has antagonistic effect on the potential sensitive channels (PSC) and the receptor operated channels (ROC). (+info)
Reversal of doxorubicin resistance by tetrandrine in Chinese hamster ovary cell line.
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Tetrandrine (Tet) 0.5 microgram.ml-1 and 1 microgram.ml-1 potentiated 2.88- and 4.3-fold growth-inhibitory effects of doxorubicin (Dox) in Chinese hamster ovary cell line (CHO), respectively, while Tet 1 microgram.ml-1 and 2.5 micrograms.ml-1 potentiated 7.3- and 8.4-fold in its resistant cell line (CHO/Dox), respectively. The colony-forming efficiencies were reduced in CHO and CHO/Dox when the cells were treated with noncytotoxic doses of Tet 2.5 micrograms.ml-1 and 5 micrograms.ml-1 in combination with different concentration of Dox. Increase in accumulation of Dox in CHO/Dox cells was shown by fluorometry. The result indicated that Tet reversed the resistance to Dox in CHO/Dox cells. (+info)
Effects of tetrandrine on action potentials and afterhyperpolarization potentials in toad dorsal root ganglia.
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Intracellular recordings were obtained from the cytosome of type A primary afferents in the isolated toad dorsal root ganglia (DRG) preparations. Bath application of Ca2+ 8.0 mmol.L-1 led to prolong action potential duration of repolarization 100% (APD100) by 23%, afterhyperpolarization potential duration of depolarization 50% (AHPD50) by 46%, and increase afterhyperpolarization potential amplitude (AHPA) by 40%. Verapamil 3 mumol.L-1 shortened the APD100 by 7% and the AHPD50 by 13%, and reduced the AHPA by 17%. The effects of Tet 3-100 mumol.L-1 consisted of APD and AHPD50 shortening and AHPA reduction in concentration-dependent manner. Tet 100 mumol.L-1, APD100 was shortened by 16%, AHPD50 by 18%, and AHPA was reduced by 20%. The results suggested that the effects of Tet may be related to its Ca2+ channel blockade in DRG. (+info)