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Biomedical subjects

K S Hsu

Publications and source records attributed to K S Hsu.

52 records · Page 3Linked to original sources
PubMed1994

Relaxation of rat thoracic aorta induced by 2,2',2''-tripyridine.

The pharmacological and toxicological activity of 2,2',2''-tripyridine was determined in rat thoracic aorta. 2,2',2''-Tripyridine inhibited norepinephrine (3 microM)-induced phasic and tonic contractions in the thoracic aorta as well as the endothelium-denuded aorta of the rat. The tonic pre-contraction elicited by norepinephrine was also relaxed by the addition of 2,2',2''-tripyridine and this relaxing effect was not affected by indomethacin (20 microM) but partially antagonized by methylene blue (50 microM). In high-K+ medium (80 mM), 2,2',2''-tripyridine inhibited the Ca2+ concentration dependent vasocontraction. Moreover, in Ca(2+)-free medium, the phasic contraction induced by either norepinephrine (3 microM) or caffeine (10 mM) was also suppressed by 2,2',2''-tripyridine. Although the cAMP level of rat aorta was not changed by 2,2',2''-tripyridine, cGMP level was significantly increased by 2,2',2''-tripyridine. The increase in cGMP level caused by 2,2',2''-tripyridine was completely blocked by methylene blue (50 microM). The 45Ca2+ influx elicited by either norepinephrine or high-K+ was inhibited by 2,2',2''-tripyridine. All of these findings indicate that 2,2',2''-tripyridine relaxes rat thoracic aorta by virtue of its Ca(2+)-channel blocking properties and by elevating cGMP levels in vascular smooth muscle.

Animals↗
PubMed1994

Blockade by MPTP of the nicotinic acetylcholine receptor channels in embryonic Xenopus muscle cells.

The effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on nicotinic acetylcholine (ACh) receptor channels were studied in cultured myocytes of 1-day-old Xenopus embryos. The amplitude and decay time of iontophoretic ACh-induced currents were reduced by MPTP in a concentration-dependent manner. The inhibitory action of MPTP was frequency-dependent, being enhanced by higher frequencies of stimulation at 7 and 30 Hz. Neither pargyline nor tranylcypromine affected the inhibitory effects of MPTP on ACh-induced currents. Single channel recordings showed that MPTP decreased the opening frequency, mean open time as well as the conductance of both low- and high-conductance ACh channels. These results suggest that the inhibitory actions of MPTP on ACh receptor channels in skeletal muscle may contribute to the depression of the nerve-evoked contraction of the mouse diaphragm as previously reported.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1994

Modification of 2,2',2''-tripyridine-induced tremor in mice by serotonergic agonists and antagonists and benzodiazepines.

The administration of 2,2',2''-tripyridine produced generalized tremor, myoclonus, and hindlimb abduction, similar to the "5-hydroxytryptamine (5-HT) syndrome," in mice. Pretreatment with mianserin, cyproheptadine, methysergide, or metergoline ameliorated, whereas 5-hydroxytryptophan (5-HTP), 5-methoxy-N,N-dimethyltryptamine (5-MeODMT), or 8-hydroxy-2-[di-n-propylamino]tetraline hydrobromide (8-OH-DPAT) augmented the 2,2',2''-tripyridine-induced tremor. Furthermore, diazepam and flunitrazepam exhibited a dose-dependent protection against 2,2',2''-tripyridine-induced tremor in mice, but pentobarbital only had a slightly protective effect. The inhibitory effects of diazepam and flunitrazepam on the 2,2',2''-tripyridine-induced tremor were potentiated in mice pretreated with p-chlorophenylalanine (PCPA). These observations suggest a serotonin-mediated action of 2,2',2''-tripyridine in its tremor action and that the benzodiazepine agonist attenuation of the 2,2',2''-tripyridine-induced tremor is probably mediated through the GABAergic inhibition of serotonergic neurons.

Animals↗
PubMed1994

Effects of bipyridylium compounds on calcium release from triadic vesicles isolated from rabbit skeletal muscle.

1. The effects of 1,1'-diheptyl-4,4'-bipyridinium dibromide (DHBP), a viologen for electrochromic memory display agent, on calcium release and ryanodine binding were studied with triad-rich sarcoplasmic reticulum (SR) vesicles isolated from rabbit skeletal muscle. 2. DHBP inhibited the calcium release induced by 2 mM caffeine and 2 micrograms ml-1 polylysine with an IC50 value of 5 micrograms ml-1 and 4 micrograms ml-1 respectively. 3. DHBP inhibited [3H]-ryanodine binding in a dose-dependent manner with an IC50 of 2.5 micrograms ml-1 and 90-100% inhibition at 20-30 micrograms ml-1. 4. Calcium uptake by SR was inhibited in the presence of caffeine and this inhibition was antagonized by concomitant addition of DHBP. 5. The effect of DHBP on muscle twitches was studied on the mouse diaphragm. Muscle twitches elicited by direct electrical muscle stimulation and contractions induced by either 10 mM caffeine or 1 microM ryanodine were blocked by pretreatment with DHBP. 6. Data from this study provided evidence that DHBP blocked the calcium release from SR by direct interaction with the calcium release channel, also known as the ryanodine receptor. A possible use of this agent as a specific inhibitor for calcium release and as a muscle relaxant was suggested.

Adenosine Triphosphatases↗
PubMed1994

Studies on the neuromuscular blocking action of commercial paraquat in mouse phrenic nerve-diaphragm.

The neuromuscular blocking actions of commercial and pure paraquat on the mouse phrenic nerve-diaphragm were compared. Twitch responses of mouse diaphragm to nerve stimulation were inhibited by commercial paraquat (5-500 microM), but not by pure paraquat (1 mM). At concentrations greater than 30 microM, commercial paraquat also directly inhibited the contractions induced by electrical stimulation of the muscle. The inhibitory actions of commercial paraquat on twitches were potentiated by pretreatment with either 0.7 microM d-tubocurarine or 2.2 microM succinylcholine. Moreover, commercial paraquat inhibited acetylcholine contracture of the denervated mouse diaphragm. Similar to d-tubocurarine, commercial paraquat protected the diaphragms from inhibition by alpha-bungarotoxin and also inhibit the binding [125I]-alpha-bungarotoxin. Electrophysiological studies revealed that commercial paraquat inhibited the amplitude of miniature end-plate potentials (m.e.p.ps) and end-plate potentials (e.p.ps) of mouse diaphragm. The inhibition induced by commercial paraquat was frequency-dependent. All of these findings indicate that commercial paraquat possesses curare-like actions and inhibits muscle contractions by binding to the postsynaptic nicotinic acetylcholine receptors. Pure paraquat does not have these effects. Analysis of the components in commercial paraquat suggested that paraquat by-products and the added emulsifying agent were responsible for these observations. The clinical significance of these findings is that this neuromuscular blocking may contribute to the respiratory failure in paraquat intoxicated patients.

Animals↗
PubMed1993

Studies on the neuromuscular blocking action of MPTP in the mouse phrenic nerve-diaphragm.

The peripheral neurotoxicity of 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) in the mouse phrenic nerve-diaphragm preparation was studied. The inhibition of nerve-evoked twitches was dependent on the concentrations of MPTP, ranging from 1 to 200 microM, which only slightly increased the amplitude of the twitch evoked by direct stimulation of the muscle. Pretreatment with pargyline did not prevent this inhibitory action of MPTP. The inhibition of the twitch by MPTP was reversible and could be partially reversed by anticholinesterase agents such as neostigmine and physostigmine, as well as ecothiophate. Pretreatment with either 0.7 microM d-tubocurarine or 2.2 microM succinylcholine, did not affect the twitches individually but markedly potentiated the effects of MPTP, by shifting the concentration-inhibition curve of MPTP to the left. MPTP not only directly inhibited acetylcholine (0.1 mM)-induced contracture of the denervated mouse diaphragm but also protected the muscle from the inhibitory action of alpha-bungarotoxin. Furthermore, the specific binding of [125I]alpha-bungarotoxin to the mouse diaphragm was also inhibited by MPTP. Electrophysiological studies revealed that MPTP inhibited the frequency and amplitude of the m.e.p.p., as well as the amplitude of the e.p.p. All of these findings indicate that MPTP exerts a neuromuscular blocking action through a curare-like action, by binding to the nicotinic acetylcholine receptors of the mouse diaphragm. The inhibitory action of MPTP on the contraction of the diaphragm is considered to play a role in the respiratory failure and muscle paralysis of intoxication with MPTP.

Analysis of Variance↗
PubMed1993

Potentiation of MPTP by 4-phenylpyridine on the neuromuscular blockade in mouse phrenic nerve-diaphragm.

Potentiation by 4-phenylpyridine (a MAO-B inhibitor) on the neuromuscular blocking action of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was studied in mouse phrenic nerve-diaphragm. MPTP blocked nerve-evoked twitches in a concentration (1-200 microM)-dependent manner. 4-Phenylpyridine, but not pargyline or tranylcypromine potentiated this inhibitory effect of MPTP. Pretreatment with 50 microM 4-phenylpyridine, reduced IC50 (concentration for 50% inhibition of twitch amplitude) values of MPTP from 53 to 18 microM and d-tubocurarine from 0.7 to 0.3 microM, respectively. 4-Phenylpyridine also enhanced the inhibitory action of MPTP and d-tubocurarine on acetylcholine (0.1 mM)-induced contracture of the denervated mouse diaphragm. The twitch inhibition induced by alpha-bungarotoxin and the specific binding of [125I]alpha-bungarotoxin to the mouse diaphragm were potentiated by 4-phenylpyridine but the inhibitory action of MPTP and d-tubocurarine on [125I]alpha-bungarotoxin binding were not significantly changed by pretreatment with 4-phenylpyridine. Electrophysiological studies revealed that the inhibitory actions of MPTP and d-tubocurarine on the amplitudes of m.e.p.ps and e.p.ps were augmented by 4-phenylpyridine. These indicate that 4-phenylpyridine enhanced the neuromuscular blocking action of the MPTP and d-tubocurarine at the postsynaptic nicotinic acetylcholine receptors. The implication of this finding is that the possible application of 4-phenylpyridine in the MPTP-induced Parkinson's disease is limited by its potentiation on the neuromuscular blocking action of MPTP.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine↗
PubMed1993

Blockade by 2,2',2''-tripyridine of the nicotinic acetylcholine receptor channels in embryonic Xenopus muscle cells.

1. The effects of 2,2',2''-tripyridine on the nicotinic acetylcholine (ACh) receptor channels were studied in the cultured myocytes of 1-day-old Xenopus embryos. 2. 2,2',2''-Tripyridine depressed the amplitude of iontophoretic ACh-induced current at a low frequency of 0.7 Hz stimulation and it not only decreased the initial responses but also enhanced the run-down of ACh-induced current at higher frequency stimulation of 7 Hz and 30 Hz. 3. Single ACh channel recordings showed that 2,2',2''-tripyridine decreased the channel conductance, the opening frequency and mean open time of both types of low- and high-conductance channels. 4. These results suggest that the blocking actions of 2,2',2''-tripyridine on ACh receptor channels in the skeletal muscle may contribute to the depression of the nerve-evoked contraction of the mouse diaphragm as reported previously.

Acetylcholine↗
PubMed1993

Muscle contracture and twitch depression induced by arsenite in the mouse phrenic nerve-diaphragm.

The purpose of this investigation was to explore the possible mechanism of muscle contracture and twitch depression induced by arsenite in the mouse diaphragm. Arsenite-contracture was dependent on extracellular Ca2+; both EGTA and Ca(2+)-channel blockers (nifedipine and verapamil) inhibited arsenite-contracture. However, the activators caffeine and ryanodine and the inhibitor ruthenium red of the Ca2+ releasing channel of sarcoplasmic reticulum (SR) all exerted a profound inhibitory action on arsenite-contracture. Neither the Ca(2+)-release nor the Ca(2+)-ATPase activity of SR. were affected by 50 microM arsenite. These findings indicate a possibility that arsenite induced muscle contracture by enhancing Ca(2+)-entry which further induced Ca(2+)-release from SR. Moreover, the possible mechanism of twitch blockade induced by arsenite was studied by an electrophysiological technique. The frequency of miniature endplate potential (m.e.p.p.) was initially increased but eventually abolished by arsenite, while the amplitude of m.e.p.p. remained unaffected and that of endplate potential rapidly declined. It is considered that arsenite increased the spontaneous release of transmitter by enhancing Ca2+ entry into the nerve terminal and inhibited the evoked transmitter release possibly by acting at a certain site which governs transmitter release.

Animals↗
PubMed1992

Studies on curare-like action of 2,2',2''-tripyridine in the mouse phrenic nerve-diaphragm.

1. The curare-like action of 2,2',2''-tripyridine (a synthetic by-product of the herbicide, paraquat) was studied in mouse phrenic nerve-diaphragm preparation. The inhibition by 2,2',2''-tripyridine of nerve-evoked twitches was dependent on the concentration, ranging from 1 to 100 microM, which had no significant effect on the twitch amplitudes evoked by direct muscle stimulation. 2. The twitch inhibition by 2,2',2''-tripyridine was reversible and could be antagonized by anticholinesterase agents such as neostigmine, physostigmine as well as ecothiophate. 3. Pretreatment with either 0.7 microM (+)-tubocurarine or 2.2 microM succinylcholine shifted the concentration-inhibition curve of 2,2',2''-tripyridine to the left. 4. 2,2'2''-Tripyridine inhibited not only acetylcholine-induced contracture of the denervated mouse diaphragm but also that of the chick biventer cervicis muscle. Like (+)-tubocurarine, 2,2',2''-tripyridine protected the twitches from the inhibition by alpha-bungarotoxin and also specifically inhibited the binding of [125I]-alpha-bungarotoxin to the mouse diaphragm. All of these findings indicate that 2,2',2''-tripyridine possesses curare-like action and inhibits the muscle contractions through binding to postsynaptic acetylcholine receptors. 5. The postsynaptic inhibition exhibited by 2,2',2''-tripyridine was also implicated in the tetanic fade, a decrease in the amplitude of miniature endplate potential (m.e.p.p.) and endplate potential (e.p.p.). 6. The clinical implication of these findings is that 2,2',2''-tripyridine may be involved in the cause of respiratory failure in paraquat-intoxicated workers since 2,2',2''-tripyridine is a by-product of paraquat synthesis.

Animals↗
PubMed1981

Effects of quinidine on atrioventricular nodal reentrant paroxysmal tachycardia.

Electrophysiologic studies were performed in 14 patients with atrioventricular nodal reentrant paroxysmal tachycardia (PSVT) before and after oral administration of 1.2-1.6 g quinidine sulfate over a 24-hour period (0.3-0.4 g every 6 hours). Studies were performed after 0.5-1 mg i.v. atropine before and after quinidine. All 14 patients had induction of sustained PSVT before quinidine, with or without atropine. After quinidine, 11 patients lost the ability to induce echoes or sustain PSVT, reflecting depression of the retrograde pathway with either absence of atrial echoes (six patients) or induction of nonsustained PSVT, with termination of echoes or PSVT occurring after QRS (block in retrograde pathway) (five patients). In only one of these 11 patients was sustained PSVT inducible after addition of atropine. All 11 were discharged on the same dose of quinidine. In three patients, quinidine was discontinued because of side effects. Follow-up in the remaining eight patients for 8 +/- 2 months showed no recurrence of sustained PSVT. Three of the 14 patients had induction of sustained PSVT after quinidine. Ventricular paced cycle length producing ventriculoatrial block was 314 +/- 7 msec (mean +/- SEM) before and 392 +/- 13 msec after quinidine (p less than 0.01) in the 14 patients, suggesting depression of the retrograde pathway with quinidine. In summary, quinidine inhibited induction of sustained atrioventricular nodal reentrant tachycardia with depression of the retrograde pathway. It is very effective in preventing recurrence of PSVT in most patients.

Adult↗
PubMed1975

Immunoelectron microscopic evidence of contractile proteins in the cellular and acellular components of mouse kidney glomeruli.

Actin and/or actin-like protein have been localized in the cellular and acellular components of the glomerular walls of mouse kidney by means of immunoelectron microscopy, employing human antibodies to smooth muscle (SMA). Contractile antigens have been confirmed to be present in the cytoplasm of podocytes and mesangial cells in association with fine filaments which are considered of importance in the control of blood flow, intravascular pressure, and filtration rate within the glomerulus. The extracellular presence of contractile proteins in the mesangial matrix and glomerular basement membrane can be related to cell movement in a frictional environment. This latter phenomenon, which is strictly interdependent with cell adhesion and aggregation, is most evident in the mesangial cells in a form of luminar pseudopodia, cytoplasmic projections, and phagocytosis.

Actins↗