Biomedical subjects

F N Ko

Publications and source records attributed to F N Ko.

At least 19 recordsLinked to original sources

PubMed2000

Antiplatelet effect of marchantinquinone, isolated from Reboulia hemisphaerica, in rabbit washed platelets.

Platelet activation is involved in serious pathological situations, including atherosclerosis and restenosis. It is important to find efficient antiplatelet medicines to prevent fatal thrombous formation during the course of these diseases. Marchantinquinone, a natural compound isolated from Reboulia hemisphaerica, inhibited platelet aggregation and ATP release stimulated by thrombin (0.1 units mL(-1)), platelet-activating factor (PAF; 2 ng mL(-1)), collagen (10 microg mL(-1)), arachidonic acid (100 microM), or U46619 (1 microM) in rabbit washed platelets. The IC50 values of marchantinquinone on the inhibition of platelet aggregation induced by these five agonists were 62.0 +/- 9.0, 86.0 +/- 7.8, 13.6 +/- 4.7, 20.9 +/- 3.1 and 13.4 +/- 5.3 microM, respectively. Marchantinquinone inhibited thromboxane B2 (TxB2) formation induced by thrombin, PAF or collagen. However, marchantinquinone did not inhibit TxB2 formation induced by arachidonic acid, indicating that marchantinquinone did not affect the activity of cyclooxygenase and thromboxane synthase. Marchantinquinone did inhibit the rising intracellular Ca2+ concentration stimulated by the five platelet-aggregation inducers. The formation of inositol monophosphate induced by thrombin was inhibited by marchantinquinone. Platelet cAMP and cGMP levels were unchanged by marchantinquinone. The results indicate that marchantinquinone exerts antiplatelet effects by inhibiting phosphoinositide turnover.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1999

Aggregation inhibitory activity of minor acetophenones from Paeonia species.

Two minor acetophenones, 2,5-dihydroxy-4-methoxy-acetophenone (2) and 2,5-dihydroxy-4-methylacetophenone (7) from Paeonia species were found to selectively inhibit the aggregation of rabbit platelets induced by arachidonic acid. They were more potent than the major compound, paeonol (1), and 7 also inhibited the formation of TXA2 and PGD2 from arachidonic acid.

Acetophenones↗

PubMed1999

Effects of prokinetic agents on contractile responses to electrical field stimulation of isolated guinea pig trachea.

We investigated the effects of two prokinetic agents, metoclopramide and cisapride, on the contractile response of isolated guinea pig tracheal segments exposed to electrical field stimulation (EFS). Tracheal segments were suspended between two platinum electrodes in organ baths. Frequency-response curves were obtained by increasing the frequency of the stimuli on equilibrated tracheal segments, in a stepwise manner. Metoclopramide potentialed the EFS-induced contraction of the tracheal; the potentiation was more prominent at lower stimulation frequencies (< or = 10 Hz). Cisapride significantly inhibited the electrically stimulated contraction in trachea strips when the frequency of the stimulus was higher than 10 Hz. In the presence of both metoclopramide and cisapride, there was a potentiation of the contractile response at lower frequencies, and this potentiation was reduced when the frequency was higher than 10 Hz. These results demonstrate that metoclopramide enhances and cisapride reduces the airway tonicity elicited by EFS in isolated guinea pig trachea segments. Further studies are needed to verify the effects of these prokinetic agents on EFS-induced contraction of isolated guinea pig trachea and to determine the mechanisms involved.

Animals↗

PubMed1998

Scavenger and antioxidant properties of prenylflavones isolated from Artocarpus heterophyllus.

The antioxidant properties of prenylflavones, isolated from Artocarpus heterophyllus Lam., was evaluated in this study. Among them, artocarpine, artocarpetin, artocarpetin A, and cycloheterophyllin diacetate and peracetate had no effect on iron-induced lipid peroxidation in rat brain homogenate. They also did not scavenge the stable free radical 1,1-diphenyl-2-picrylhydrazyl. In contrast, cycloheterophyllin and artonins A and B inhibited iron-induced lipid peroxidation in rat brain homogenate and scavenged 1,1-diphenyl-2-picrylhydrazyl. They also scavenged peroxyl radicals and hydroxyl radicals that were generated by 2,2'-azobis(2-amidinopropane) dihydrochloride and the Fe3+-ascorbate-EDTA-H2O2 system, respectively. However, they did not inhibit xanthine oxidase activity or scavenge superoxide anion, hydrogen peroxide, carbon radical, or peroxyl radicals derived from 2,2'-azobis(2,4-dimethylvaleronitrile) in hexane. Moreover, cycloheterophyllin and artonins A and B inhibited copper-catalyzed oxidation of human low-density lipoprotein, as measured by fluorescence intensity, thiobarbituric acid-reactive substance and conjugated-diene formations and electrophoretic mobility. It is concluded that cycloheterophyllin and artonins A and B serve as powerful antioxidants against lipid peroxidation when biomembranes are exposed to oxygen radicals.

Animals↗

PubMed1998

Antioxidant properties of butein isolated from Dalbergia odorifera.

The antioxidant properties of butein, isolated from Dalbergia odorifera T. Chen, were investigated in this study. Butein inhibited iron-induced lipid peroxidation in rat brain homogenate in a concentration-dependent manner with an IC50, 3.3+/-0.4 microM. It was as potent as alpha-tocopherol in reducing the stable free radical diphenyl-2-picrylhydrazyl (DPPH) with an IC0.200, 9.2+/-1.8 microM. It also inhibited the activity of xanthine oxidase with an IC50, 5.9+/-0.3 microM. Besides, butein scavenged the peroxyl radical derived from 2,2-azobis(2-amidinopropane) dihydrochloride (AAPH) in aqueous phase, but not that from 2,2-azobis(2, 4-dimethylvaleronitrile) (AMVN) in hexane. Furthermore, butein inhibited copper-catalyzed oxidation of human low-density lipoprotein (LDL), as measured by conjugated dienes and thiobarbituric acid-reactive substance (TBARS) formations, and electrophoretic mobility in a concentration-dependent manner. Spectral analysis revealed that butein was a chelator of ferrous and copper ions. It is proposed that butein serves as a powerful antioxidant against lipid and LDL peroxidation by its versatile free radical scavenging actions and metal ion chelation.

Animals↗

PubMed1998

Isoorientin-6"-O-glucoside, a water-soluble antioxidant isolated from Gentiana arisanensis.

The antioxidant activities of isoorientin-6"-O-glucoside were studied using various models. Isoorientin-6"-O-glucoside was more potent than Trolox, probucol and butylated hydroxytoluene (BHT) in reducing the stable free radical 1,1-diphenyl-2-picrylhydrazyl (DPPH). It also scavenged superoxide anion, peroxyl and hydroxyl radicals that were generated by xanthine/xanthine oxidase, 2,2'-azobis(2-amidinopropane) dihydrochloride (AAPH) and Fe3+-ascorbate-EDTA-H2O2 system, respectively. The IC50 value, stoichiometry factor and second-order rate constant were 9.0+/-0.8 microM, 1.8+/-0.1 and 2.6 X 10(10) M(-1) s(-1) for superoxide generation, peroxyl and hydroxyl radicals. However, isoorientin-6"-O-glucoside did not inhibit xanthine oxidase activity or scavenge hydrogen peroxide (H2O2), carbon radical or 2,2'-azobis(2,4-dimethyl-valeronitrile) (AMVN)-derived peroxyl radical in hexane. Isoorientin-6"-O-glucoside inhibited Cu2+-induced oxidation of human low-density lipoprotein (LDL) as measured by fluorescence intensity, thiobarbituric acid-reactive substance formation and electrophoretic mobility. Since isoorientin-6"-O-glucoside did not possess pro-oxidant activity, it may be an effective water-soluble antioxidant that can prevent LDL against oxidation.

Antioxidants↗

PubMed1998

Antiproliferative effect in human prostatic smooth muscle cells by nitric oxide donor.

We obtained a primary culture of prostatic cells through explantation from patients with benign prostatic hyperplasia. Structural morphology, immunohistochemical staining, and growth characteristics of these cells demonstrate that they are consistent with the population of smooth muscle cells (SMCs). We examined the influence of a nitric oxide donor, sodium nitroprusside (SNP), on the regulation of human prostatic SMC proliferation. SNP exhibited a concentration-dependent (0.1-10 microM) inhibition of fetal calf serum-induced proliferation in human prostatic SMCs. In addition, growth-inhibitory responses to 8-bromo-cGMP (1-30 muM) were observed. However, the responses to SNP were significantly diminished by the presence of 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (3 microM; a selective guanylate cyclase inhibitor). Furthermore, SNP induced an increased concentration-dependent accumulation of intracellular cGMP in human prostatic SMCs. After 48-hr period of deprivation of serum, cells were restimulated with serum to permit cell cycle progression. The addition of SNP (10 microM) at various times after the addition of serum to serum-deprived cells showed maximal inhibition of cell proliferation even when added 6 hr after the serum. This blocking effect of cell cycle progression was lost gradually as the delay from serum to SNP application increased from 6 to 18 hr. The membrane-associated protein kinase C (PKC) activity was studied in human prostatic SMCs; results showed that fetal calf serum (10%, v/v) significantly increased membrane-associated PKC activity. SNP (10 muM), which had little effect on basal kinase activity, completely abolished serum-induced augmentation of PKC activity. Therefore, we suggest that SNP mediates its antiproliferative effect by the inhibition of PKC activity on human prostatic SMCs; furthermore, its antiproliferative effect occurs at the early G1 phase of the cell cycle.

Apoptosis↗

PubMed1998

Antiplatelet action of 3',4'-diisovalerylkhellactone diester purified from Peucedanum japonicum Thunb.

3',4'-Diisovalerylkhellactone diester (PJ-1) is a coumarin derivative purified from the medicinal herb Peucedanum japonicum Thunb. We examined its in vitro effects on various aspects of platelet reactivity. PJ-1 inhibited the aggregation and ATP release of rabbit platelets induced by PAF (platelet-activating factor) and collagen. The IC50 values of PJ-1 and BN52021 on PAF (2 ng/ml)-induced platelet aggregation were about 56.3 and 22.0 microM, respectively. And, the IC50 value of PJ-1 toward collagen (10 microg/ml)-induced platelet aggregation was 89.4 microM. Although the platelet aggregation caused by arachidonic acid and thrombin were barely inhibited by PJ-1, the release reactions were partially suppressed. PJ-1 also inhibited the thromboxane B2 formation caused by collagen, while formations of thromboxane B2 and prostaglandin D2 caused by arachidonic acid were not affected. The phosphoinositide breakdown caused by PAF was inhibited by PJ-1, but those by other inducers were not affected significantly. PJ-1 inhibited the intracellular Ca2+ increase caused by PAF in fura-2-loaded platelets. PJ-1 also concentration-dependently inhibited [3H]PAF (3.03 ng/ml) binding to washed platelets with an IC50 value of 3.9 microM. It is concluded that the main antiplatelet effect of PJ-1 may be due to dual activities on the blockade of PAF receptor-induced activation and also the inhibition of phospholipase A2 in rabbit platelets.

Adenosine Triphosphate↗

PubMed1998

Effect of PP1D-1, a synthetic antiplatelet compound, on rabbit platelets.

The antiplatelet mechanism of a synthetic compound, 2-chloro-3-methoxycarbonylpropionamido-1,4-naphthoquinone (PP1D-1), was studied by employing washed rabbit platelets in vitro. PP1D-1 concentration-dependently inhibited thrombin (0.1 U/ml)-, platelet-activating factor (2 ng/ml)-, collagen (10 microg/ml)-, arachidonic acid (100 microM)- and U46619 (1 microM)-induced aggregation and ATP release in washed rabbit platelets. The IC50 values of PP1D-1 for aggregation induced by the above inducers are 17.9+/-1.7, 9.8+/-1.1, 3.9+/-0.4, 1.8+/-0.3 and 1.7+/-0.3 microM, respectively. PP1D-1 did not affect platelet thromboxane B2 or prostaglandin D2 formation induced by arachidonic acid, indicating that it did not affect cyclooxygenase and thromboxane synthase activities. PP1D-1 significantly inhibited the formation of inositol 1,4,5-trisphosphate caused by these five platelet stimulators. Moreover, PP1D-1 inhibited the increase in intracellular calcium concentration induced by these agents. On the contrary, PP1D-1 did not inhibit thapsigargin-elevated intracellular calcium concentration in indomethacin-pretreated platelets, indicating it did not influence the effect of thapsigargin. According to these data, PP1D-1 exerts antiplatelet effects mainly by inhibiting phosphoinositide turnover.

Adenosine Triphosphate↗

PubMed1998

Antiplatelet agents isolated from medicinal plants.

Platelet-vessel wall interaction is an important process in physiological hemostasis and pathological thrombosis. In oriental countries, some medicinal plants have been claimed for uses to improve circulation, induce fibrinolysis or prevent thrombosis. In cooperation with chemists using bioassay-based step-by-step purification, some antiplatelet agents were isolated from plant sources. According to their effects on platelet aggregation, release reaction and signal transductions involved, these antiplatelet agents can be classified into eight groups: 1. platelet-activating factor (PAF) antagonists, 2. collagen-receptor antagonists, 3. thromboxane-receptor antagonists, 4. ADP-receptor agonists, 5. inhibitors of phosphoinositide breakdown, 6. inhibitors of thromboxane formation, 7. agents increasing cyclic nucleotides, and 8. protein kinase C activators. These new pharmacological agents derived from medicinal plant sources may be useful as leads to develop as effective cardiovascular drugs.

Animals↗

PubMed1997

Inhibition of platelet adhesion to collagen by cGMP-elevating agents.

In the present study, we examined the effects and action mechanisms of cGMP-elevating agents on platelet adhesion to collagen fiber. YC-1, a nitric oxide (NO)-independent activator of soluble guanylate cyclase, inhibited both initial and long-term platelet adhesion to collagen, and the inhibitory effect was potentiated by dipyridamole, a selective inhibitor of cGMP-specific phosphodiesterase. Sodium nitroprusside (SNP), a NO-donor, and 8-bromo-cGMP also inhibited the initial platelet adhesion, but inhibited long-term adhesion only in the presence of dipyridamole. Collagen-induced intracellular Ca2+ mobilization and actin polymerization were prevented by YC-1, SNP and 8-bromo-cGMP. Since blockade of Ca2+ mobilization and actin polymerization caused by collagen led to decrease of platelet adhesion, we suggest that the inhibitory activity of cGMP-elevating agents on the adhesion of platelets to collagen is resulting from interference of these signaling pathways.

Actins↗

PubMed1997

YC-1, a nitric oxide-independent activator of soluble guanylate cyclase, inhibits platelet-rich thrombosis in mice.

YC-1 (3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole), a nitric oxide (NO)-independent activator of soluble guanylate cyclase, has been shown to inhibit platelet activation and aggregation in vitro through the generation of cGMP. In the present study, we assessed the antithrombotic effect of YC-1 in models of experimental thrombosis in mice. YC-1 (10, 30 micrograms/g, i.p.)-treated mice showed a prolonged tail bleeding time 30 min after injection (from control 91.0 +/- 6.4 s to 208.6 +/- 22.7 s and 291.8 +/- 42.4 s, respectively). In contrast, aspirin at a dose of 30 micrograms/g (i.p.) prolonged the bleeding time to more than 600 s. Platelet-rich thrombus formation was induced by irradiation of the mesenteric venule with filtered light in mice pretreated intravenously with fluorescein sodium. YC-1 (30 micrograms/g, i.p.) markedly prolonged the occlusion time of irradiated venules (from control 146.1 +/- 19.0 s to 275.6 +/- 24.5 s) in heparinized (1 U/g) mice. In the same condition, aspirin (100 micrograms/g) only slightly prolonged the time required for occlusion (193.2 +/- 13.2 s). In a model of fatal pulmonary thromboembolism induced by intravenous injection of ADP (300 micrograms/g), YC-1 was effective in reducing mortality when administered intraperitoneally at doses of 10-30 micrograms/g. The antithrombotic effect of YC-1 was correlated with the inhibition of ADP-induced platelet aggregation ex vivo. In contrast, aspirin (30, 100 micrograms/g) did not inhibit ADP-induced pulmonary thromboembolism in vivo or platelet aggregation ex vivo. YC-1 (3, 10 micrograms/g) also exhibited profibrinolytic activity ex vivo, as revealed by shortening of the euglobulin clot lysis time. Therefore, YC-1 is an effective antithrombotic agent in preventing thrombosis in animal models, and its antiaggregating and additional profibrinolytic effects may be of potential clinical benefit in the treatment of thromboembolic diseases.

Adenosine Diphosphate↗

PubMed1997

The effect of the selective PAF antagonist CIS-19 on PAF- and antigen-induced bronchoconstriction, microvascular leakage and bronchial hyperreactivity in guinea-pigs.

We investigated the effects of a novel platelet-activating factor (PAF) receptor antagonist, CIS-19 [cis-2-(3, 4-dimethoxyphenyl)-6-isopropoxy-7-methoxy-1-(N-methyl-formamido)-1, 2, 3, 4-tetrahydronaphthalene], on PAF-, histamine-, substance P- and antigen-induced bronchoconstriction and microvascular leakage, as well as PAF- and antigen-induced bronchial hyperreactivity to methacholine in urethane-anesthetized guinea-pigs. Administration of CIS-19 (0.5-5 mg/kg, i.v.) inhibited the increase in lung resistance induced by PAF (30 ng/kg, i.v.) in a dose-dependent manner, but failed to inhibit the increase induced by histamine (30 micrograms/kg, i.v.) or substance P (6.5 micrograms/kg, i.v.). CIS-19 (5 mg/kg, i.v.) did not inhibit the increase in lung resistance induced by ovalbumin (2 mg/kg, i.v.) in actively sensitized guinea-pigs. PAF (30 ng/kg, i.v.)-induced microvascular leakage, measured by the extravasation of Evans blue dye, was dose-dependently inhibited by CIS-19 (0.5-5 mg/kg, i.v.) in the trachea, main bronchi and intrapulmonary airways, but it did not affect histamine (30 micrograms/kg, i.v.)- or substance P (6.5 micrograms/kg, i.v.)-induced microvascular leakage at all airway levels. CIS-19 (2.5 and 5 mg/kg) did not affect ovalbumin (2 mg/kg, i.v.)-induced microvascular leakage in all airway levels in actively sensitized guinea-pigs, CIS-19 (2.5 and 5 mg/kg, i.v.) significantly inhibited PAF-induced enhancement of the bronchial response to methacholine, but had no effect on ovalbumin (0.05 mg/kg, i.v.)-induced bronchial hyperreactivity in actively sensitized guinea-pigs. It is concluded that CIS-19 is a potent PAF receptor antagonist which inhibits PAF- but not antigen-induced bronchoconstriction, microvascular leakage and bronchial hyperreactivity. These results suggest that PAF plays little or no role in early airway responses following antigen challenge.

Airway Resistance↗

PubMed1997

Protection of oxidative hemolysis by demethyldiisoeugenol in normal and beta-thalassemic red blood cells.

The purpose of this study was to evaluate the ability of demethyldiisoeugenol to protect normal and beta-thalassemic human red blood cells (RBCs) against oxidative damage in vitro. Oxidative hemolysis and lipid peroxidation of normal and beta-thalassemic human RBCs induced by aqueous peroxyl radical were suppressed by demethyldiisoeugenol in a concentration-dependent manner. The formation of proteins with high molecular weight and concomitant decrease of the low-molecular-weight proteins of RBCs challenge with aqueous peroxyl radical were inhibited by demethyldiisoeugenol. It also prevented the shortening of the Russell's viper venom (RVV)-clotting time mediated by prelytic radical-treated RBCs. In contrast, demethyldiisoeugenol inhibited oxidative hemolysis but not those metHb and ferrylHb formations caused by hydrogen peroxide (H2O2) in normal RBCs. Furthermore, demethyldiisoeugenol did not prevent the consumption of the cytosolic antioxidant, glutathione (GSH), in radical-treated RBCs. It also did not cause of a loss of sulfhydryl group during incubation with GSH. However, the diphenyl-2-picrylhydrazyl (DPPH) scavenging activity of demethyldiisoeugenol was dramatically increased in the presence of GSH. These results imply that demethyldiisoeugenol can regenerate from its oxidized form to its active reduced form in the presence of GSH. It may be useful in diminishing oxidative damage to pathological RBCs.

Amidines↗

PubMed1997

A new flavone C-glycoside and antiplatelet and vasorelaxing flavones from Gentiana arisanensis.

A new flavone C-glycoside, isovitexin 6"-O-glucoside (1), and three known flavonoids, quercetin, isovitexin, and luteolin-7-O-beta-D-glucoside, have been further isolated from the whole plant of Gentiana arisanensis Hayata. The new compound was characterized by spectral methods and chemical reactions. The antiplatelet effects of isovitexin 6"-O-glucoside (1), isoorientin (2), 2 peracetate (3), isovitexin (4), luteolin 7-O-beta-D-glucoside (5), luteolin (6), isoorientin 6"-O-glucoside (7), and 7 peracetate (8) were studied using washed rabbit platelets. Of the compounds tested, 6 showed potent antiplatelet effects on arachidonic acid (AA)-induced platelet aggregation (IC50 = 43.5 microM). The effect of 2, 5, and 6 on the contraction of rat thoracic aorta was also studied. Compound 6 depressed markedly the contraction induced by Ca2+ (1.9 mM) in high-K+ (80 mM) medium, with an IC50 of about 156 microM and also inhibited noradrenaline (3 microM)-induced phasic and tonic contractions, with an IC50 of about 68 and 72 microM, respectively.

Animals↗

PubMed1997

Bioactive alkaloids from Illigera luzonensis.

Using antiplatelet aggregation as a guide to fractionation, seven aporphines, actinodaphnine (1), N-methylactinodaphnine (2), launobine (3), dicentrine (4), O-methylbulbocapnine (5), hernovine (7), and bulbocapnine (9), and two oxoaporphines, dicentrinone (6) and liriodenine (8), were isolated from the stems of Illigera luzonensis. Among them, compounds 2, 4, 5, 8, and 9 were isolated for the first time from this species. Moreover, compounds 1-5, and 8 showed significant antiplatelet aggregation and compounds 1 and 6 exhibited significant vasorelaxant activities, respectively.

Alkaloids↗

PubMed1997

Bioactive constituents of Morus australis and Broussonetia papyrifera.

The biological activities of the active principles of two plants in the Moraceae have been investigated. A new prenylflavonoid, australone A (1), and a new triterpenoid, 3 beta-[(m-methoxybenzoyl)oxy]urs-12-en-28-ioc acid (2) were isolated from the root bark of Morus australis, and their structures determined by spectroscopic methods. Also isolated from this plant were seven known compounds, morusin (3), kuwanon C (4), betulinic acid, beta-amyrin, quercetin, ursolic acid, and compound A. Morusin (3) showed significant effects on arachidonic acid-, collagen-, and PAF-induced platelet aggregation, while kuwanon C (4) was active in the arachidonic acid- and PAF-induced platelet aggregation assays. In biological work on a second plant, Broussonetia papyrifera, broussoflavonols F (5) and G (6), broussoflavan A (7), and broussoaurone A (8) potently inhibited Fe(2+)-induced lipid oxidation in rat-brain homogenate. Compounds 5-7 also significantly inhibited the proliferation of rat vascular smooth muscle cells.

Animals↗

PubMed1997

Activation by high potassium of a novel voltage-operated Ca2+ channel in rat spleen.

1. High potassium produced a concentration-dependent contraction in rat isolated spleen. 2. The high potassium-induced contraction of rat spleen was abolished in Ca(2+)-free Krebs solution containing 1 mM EGTA, and the subsequent addition of 3 mM Ca2+ restored the high potassium-induced contraction to the control level. 3. Nifedipine, verapamil, diltiazem, Cd2+, Ni2+, Co2+, R-(+)-Bay K 8644 and pimozide inhibited and relaxed high potassium-induced contraction of rat spleen with IC50 and EC50 values much higher than those values in rat aorta. 4. In addition, high potassium-stimulated contraction of rat spleen was insensitive to omega-conotoxin GVIA, omega-conotoxin MVIIC and omega-agatoxin IVA. 5. The high potassium-induced contraction of rat spleen was also unaffected by tetrodotoxin (TTX), prazosin, chloroethylclonidine (CEC), yohimbine, propranolol, atropine, diphenhydramine, cimetidine, ketanserin, 3-tropanyl-indole-3-carboxylate, saralasin, indomethacin, nordihydroguaiaretic acid, GR32191B, domperidone, naloxone, chlorpromazine, suramin, (+/-)-2-amino-5-phosphonopentanoic acid, 6,7-dinitroquinoxaline-2,3-dione (DNQX), L-659,877, L-703,606, lorglumide, PD 135,158 N-methyl-D-glucamine, benextramine, amiloride, dantrolene, TMB-8, econazole, staurosporine and neomycin. 6. Forskolin and sodium nitroprusside relaxed high potassium-induced contraction of rat spleen with EC50 values of 0.55 +/- 0.04 and 20.0 +/- 2.7 microM, respectively. 7. It is concluded that high potassium may activate a novel, pharmacologically uncharacterized voltage-operated Ca2+ channel in rat spleen.

Animals↗