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F N Ko

Publications and source records attributed to F N Ko.

At least 109 records · Page 6Linked to original sources
PubMed1993

Pharmacological activity of (-)-discretamine, a novel vascular alpha-adrenoceptor and 5-hydroxytryptamine receptor antagonist, isolated from Fissistigma glaucescens.

1. The pharmacological activity of (-)-discretamine, isolated from Fissistigma glaucescens, was determined in rat isolated thoracic aorta, cardiac tissues and ventricular myocytes and guinea-pig isolated trachea. 2. (-)-Discretamine was found to be an alpha 1-adrenoceptor blocking agent in rat thoracic aorta as revealed by its competitive antagonism of noradrenaline (pA2 = 7.20 +/- 0.10)- or phenylephrine (pA2 = 7.60 +/- 0.09)-induced vasoconstriction. It was as potent as phentolamine (pA2 = 7.51 +/- 0.10), but was more potent than yohimbine (pA2 = 6.18 +/- 0.06). Removal of endothelium significantly increased the antagonistic potency of (-)-discretamine on noradrenaline (pA2 = 7.52 +/- 0.09)- or phenylephrine (pA2 = 7.90 +/- 0.09)-induced vasoconstriction. 3. (-)-Discretamine was also an alpha 2-adrenoceptor blocking agent (pA2 = 6.30 +/- 0.15) and a 5-hydroxytryptamine antagonist (pA2 = 6.87 +/- 0.06), both in rat aorta denuded of endothelium. 4. (-)-Discretamine protected alpha-adrenoceptors from alkylation by the irreversible blocking agent, phenoxybenzamine. 5. [3H]-inositol monophosphate formation caused by noradrenaline (3 microM) in rat thoracic aorta was suppressed by (-)-discretamine (10 and 30 microM) and prazosin (3 microM). 6. A high concentration of (-)-discretamine (30 microM) did not affect the contraction induced by the thromboxane receptor agonist U-46619, prostaglandin F2 alpha (PGF2 alpha), angiotensin II, high K+ or endothelin in rat aorta denuded of endothelium. Neither cyclic AMP nor cyclic GMP content of rat thoracic aorta was changed by (-)-discretamine. 7. Contraction of guinea-pig trachea caused by histamine, leukotriene C4 or carbachol was not affected by (-)-discretamine (30 microM). (-)-Discretamine also did not block beta l- or beta2-adrenoceptor-mediated responses induced by isoprenaline in rat right atria and guinea-pig trachea.8. A voltage clamp study in rat ventricular single myocytes revealed that sodium inward current, slow inward Ca2+ current or transient (ItO) and steady state (I800) outward current was not affected by(-)-discretamine (30 microM).9. It is concluded that (-)-discretamine is a selective x-adrenoceptor and 5-HT receptor antagonist in vascular smooth muscle.

Adrenergic alpha-Antagonists↗
PubMed1993

Ca(2+)-channel blockade in rat thoracic aorta by crychine isolated from Cryptocarya chinensis Hemsl.

The pharmacological effects of crychine, isolated from Cryptocarya chinensis Hemsl, on rat thoracic aorta were examined. In the high-K+ medium (60 mM), Ca2+ (0.03-3 mM)-induced vasoconstriction was inhibited by crychine in a concentration-dependent manner (10-100 micrograms mL-1). Increasing the incubation time from 5 to 30 min did not cause more pronounced inhibitory effect on KCl-induced contraction. The tonic contractions elicited by KCl (60 mM) and Bay K 8644 (0.1 microM) were also relaxed by the addition of crychine and were more marked in the 1.9 mM than in the 5 mM Ca2+ medium. The noradrenaline concentration-response curves were antagonized non-competitively by crychine (10-100 micrograms mL-1). At the plateau of noradrenaline-induced tonic contraction, the addition of crychine also caused relaxation. This relaxing effect of crychine was not antagonized by indomethacin (20 microM) or methylene blue (50 microM), and was still present in denuded aorta or in the presence of nifedipine (2 microM). Caffeine (10 mM)-induced contraction and cAMP or cGMP levels were not affected by crychine. It is concluded that crychine relaxes the rat thoracic aorta mainly by suppressing the Ca2+ influx through both voltage- and receptor-operated calcium channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1992

Vasorelaxation of rat thoracic aorta caused by osthole isolated from Angelica pubescens.

The pharmacological effects of osthole on isolated rat thoracic aorta were examined. Osthole inhibited norepinephrine (NE, 3 microM)-induced phasic and tonic contractions in rat thoracic aorta in a concentration-dependent manner (40-200 microM). The tonic contraction elicited by NE was also relaxed by the addition of osthole. This relaxing effect of osthole was not affected by indomethacin (20 microM) and was still observed in endothelium-denuded rat aorta. Methylene blue (50 microM) partially antagonized this relaxing effect of osthole. In high-K+ medium (80 mM), the Ca2+ (0.03-3 mM)-induced vasocontraction was inhibited concentration dependently by osthole (20-100 microM). Addition of osthole (100 microM) at the plateau of the K+ (80 mM)-induced contraction caused relaxation. Methylene blue (50 microM) did not antagonize this relaxation. In Ca(2+)-free medium, the caffeine (10 mM)-induced phasic contraction was also suppressed by osthole in a concentration-dependent manner. Although the cAMP level was not changed by osthole, the cGMP level of rat aorta was increased by osthole in a concentration-dependent manner. The increase in cGMP level caused by osthole was completely blocked by methylene blue. [3H]Inositol monophosphate formation caused by NE was not affected by osthole at a concentration of 200 microM. The 45Ca2+ influx elicited by either NE or high K+ was inhibited by osthole in a concentration-dependent manner. It is concluded that osthole relaxes rat thoracic aorta by virtue of its Ca(2+)-channel blocking properties and by elevating cGMP levels in vascular smooth muscle.

Animals↗
PubMed1992

PAF antagonism in vitro and in vivo by aglafoline from Aglaia elliptifolia Merr.

Aglafoline, isolated from Aglaia elliptifolia Merr, inhibited in a selective and concentration-dependent manner the aggregation and ATP release reaction induced in washed rabbit platelets by PAF (platelet-activating factor). The IC50 values of aglafoline, BN52021 and kadsurenone on PAF (3.6 nM)-induced platelet aggregation were about 50, 12 and 18 microM, respectively. Aglafoline also inhibited [3H]PAF (3.6 nM) binding to washed rabbit platelets with an IC50 value of 17.8 +/- 2.6 microM. The concentration-response curve of PAF-induced platelet aggregation was shifted to the right by aglafoline with pA2 and pA10 values of 5.97 and 5.04, respectively. Although thromboxane B2 formation caused by collagen and thrombin was partially suppressed by aglafoline, thromboxane B2 formation caused by ionophore A23187 and arachidonic acid was not affected. Aglafoline inhibited the [3H]inositol monophosphate formation caused by PAF but not that caused by collagen or thrombin in the presence of indomethacin (20 microM). The cAMP content of washed rabbit platelets was not affected by aglafoline. Rat femoral intravenous administration of aglafoline (10 mg/kg) did not affect blood pressure. However, aglafoline (10 mg/kg) both prophylactically and therapeutically antagonized PAF (2.5 micrograms/kg)-induced hypotensive shock in rats. Intravenous PAF (30 ng/kg) caused severe bronchoconstriction in guinea pigs. This effect was completely blocked by aglafoline. This implies aglafoline is an effective PAF antagonist not only in vitro, but also in vivo.

Adenosine Triphosphate↗
PubMed1992

Dicentrine, a novel antiplatelet agent inhibiting thromboxane formation and increasing the cyclic AMP level of rabbit platelets.

Dicentrine is an antiplatelet agent isolated from the Chinese herb Lindera megaphylla. We examined the in vitro effects of dicentrine on various aspects of platelet reactivity. Dicentrine inhibited the aggregation and ATP release of washed rabbit platelets induced by arachidonic acid (AA), collagen, ADP, platelet-activating factor (PAF), thrombin and U46619. Dicentrine also inhibited the thromboxane B2 formation caused by AA, collagen and thrombin in washed intact platelets or that induced by AA in lysed platelet homogenate, while prostaglandin D2 formation caused by AA was not increased. The generation of inositol monophosphates (in the presence of indomethacin) caused by thrombin, collagen and PAF was not suppressed significantly, nor did dicentrine suppress fibrinogen-induced aggregation of elastase-treated platelets. Dicentrine inhibited the intracellular Ca2+ increase in quin-2/AM-loaded platelets caused by thrombin, PAF, collagen and AA. The cyclic AMP level was elevated by dicentrine in a concentration-dependent manner. These data indicate that the inhibitory effect of dicentrine on platelet aggregation and ATP release was due to the inhibition of thromboxane formation and the elevation of the level of cyclic AMP.

Adenosine Triphosphate↗
PubMed1992

Gamma-pyrone compounds. II: Synthesis and antiplatelet effects of tetraoxygenated xanthones.

Norathyriol and its analogues, 1,3,5,6-, 3,4,5,6-, 3,4,6,7- and 2,3,6,7-tetrahydroxyxanthone, were synthesized from benzophenone precursors by Friedel-Crafts acylation and subsequent base-catalyzed cyclization to eliminate methanol. Both 3,4,6,7- and 2,3,6,7-tetrahydroxyxanthone tetraacetate showed potent anti-platelet aggregation effects on arachidonic acid-induced platelet aggregation. 3,4,6,7-Tetrahydroxyxanthone tetraacetate and 1,3,5,6-tetrahydroxyxanthone showed potent and significant anti-platelet aggregation effects on collagen-induced platelet aggregation.

Adenosine Diphosphate↗
PubMed1992

Vasorelaxing effect in rat thoracic aorta caused by fraxinellone and dictamine isolated from the Chinese herb Dictamnus dasycarpus Turcz: comparison with cromakalim and Ca2+ channel blockers.

The components of Dictamnus dasycarpus Turcz were tested for their vasorelaxing effect on the rat aorta, and fraxinellone and dictamine were shown to be effective vasorelaxants. In high K+ (60 mmol/l) medium, Ca2+ (0.03 to 3 mmol/l)-induced vasoconstriction was inhibited concentration-dependently by both agents. The IC50 for fraxinellone and dictamine were calculated to be about 25 mumol/l and 15 mumol/l (for Ca2+ concentration of 1 mmol/l), respectively. Cromakalim (0.2-10 mumol/l) relaxed aortic rings precontracted with 15 but not 60 mmol/l of K+. Fraxinellone and verapamil were more potent and effective in producing relaxation in 60 mmol/l than in 15 mmol/l K(+)-induced contraction. However, dictamine was more potent in producing relaxation in 15 mmol/l K(+)-induced contraction. Nifedipine (1 mumol/l), dictamine (100 mumol/l) and fraxinellone (100 mumol/l) relaxed the aortic contraction caused by KCl or Bay K 8644. The tonic contraction elicited by noradrenaline (NA, 3 mumol/l) was also relaxed by dictamine (500 mumol/l), but not by fraxinellone (500 mumol/l) in the nifedipine (1 mumol/l)-treated aorta. This relaxing effect of dictamine persisted in endothelium-denuded aorta. Glibenclamide (10 mumol/l) shifted the concentration-relaxation curve of cromakalim, but not that of dictamine, to the right in rat aortic rings precontracted with NA. Dictamine (500 mumol/l) did not affect tonic contraction of NA which are reduced by H-7 (1 mumol/l) in Ca(2+)-depleted medium. In conclusion, fraxinellone is a selective blocker of voltage-dependent Ca2+ channel, while dictamine relaxed the rat aorta by suppressing the Ca2+ influx through both voltage-dependent and receptor-operated Ca2+ channels.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1992

Haemodynamic effects of dicentrine, a novel alpha 1-adrenoceptor antagonist: comparison with prazosin in spontaneously hypertensive and normotensive Wistar-Kyoto rats.

1. The haemodynamic effects of dicentrine, an aporphine derivative isolated from the plant Lindera megaphylla, were investigated and compared with prazosin in rats. 2. In anaesthetized normotensive Wistar-Kyoto (WKY) rats, i.v. administration of dicentrine (0.1, 0.5, 1.0 mg kg-1) and prazosin (0.01, 0.05, 0.1 mg kg-1) induced a dose-related reduction of mean arterial pressure (MAP) which reached a maximal effect 5-10 min after injection and persisted for 2 h. 3. In anaesthetized WKY rats, a higher dose of dicentrine (1.0 mg kg-1, i.v.) did not cause any significant changes in heart rate (HR), cardiac output (CO) and stroke volume (SV) but markedly increased tail blood flow. In contrast, a higher dose of prazosin (0.1 mg kg-1, i.v.) produced a decrease in HR which paralleled the time course of the hypotensive response. 4. The hypotensive activity of dicentrine was completely abolished by alpha-adrenoceptor blockade. Both dicentrine and prazosin significantly attenuated pressor responses to noradrenaline but failed, even at maximal hypotensive doses, to impair the pressor effects of angiotensin II or vasopressin. These observations suggest that dicentrine appears to exert its hypotensive action through alpha 1-adrenoceptor blockade. 5. In conscious normotensive and spontaneously hypertensive (SH) rats, dicentrine (0.5-2.0 mg kg-1, i.v.) and prazosin (0.05-0.2 mg kg-1, i.v.) also evoked dose-related decreases in MAP which were of greater magnitude in SH rats. Oral administration of dicentrine (5 and 8 mg kg-1) to conscious SH rats caused a hypotensive effect which persisted for over 15 h.6. These results suggest that dicentrine may have therapeutic potential as an oral antihypertensive drug via alpha-adrenoceptor blockade.

Adrenergic alpha-Antagonists↗
PubMed1992

Ca(2+)-channel blockade in rat thoracic aorta by protopine isolated from Corydalis tubers.

The pharmacological properties and mechanism of the action of protopine on isolated rat thoracic aorta were examined. It inhibited norepinephrine (NE, 3 microM)-induced tonic contraction in rat thoracic aorta in a concentration-dependent manner (25-100 micrograms/ml). The phasic contraction caused by NE was inhibited only by a high concentration of protopine (100 micrograms/ml). At the plateau of NE-induced tonic contraction, the addition of protopine also caused relaxation. This relaxing effect of protopine was not antagonized by indomethacin (20 microM) or methylene blue (50 microM), and it still existed in denuded rat aorta or in the presence of nifedipine (2-100 microM). Protopine also inhibited high potassium (60 mM)-induced, calcium-dependent (0.03-3 mM) contraction of rat aorta in a concentration-dependent manner. Neither cAMP nor cGMP level was changed by protopine. Both the formation of inositol monophosphate caused by NE and the phasic contraction induced by caffeine were also not affected by protopine. 45Ca2+ influx caused by either NE or K+ was inhibited by protopine concentration-dependently. It is concluded that protopine relaxed the rat thoracic aorta mainly by suppressing the Ca2+ influx through both voltage- and receptor-operated calcium channels.

Alkaloids↗
PubMed1991

Comparison of the actions of some platelet-activating factor antagonists on platelets and aortic smooth muscles.

The pharmacological actions of five platelet-activating factor (PAF) antagonists were compared in rabbit platelets and rat thoracic aorta. In PAF (2 ng/ml)-induced aggregation of washed rabbit platelets, WEB 2086 and WEB 2170 much were more potent inhibitors than BN 52021, kadsurenone and denudatin B, and the IC50 values were calculated to be 0.1, 0.3, 5, 8 and 10 micrograms/ml, respectively. WEB 2086, WEB 2170 and BN 52021 did not affect the platelet aggregation caused by collagen (10 micrograms/ml), ADP (20 microM), arachidonic acid (100 microM) or thrombin (0.1 U/ml). Kadsurenone and denudatin B suppressed ATP release, thromboxane B2 formation and the rise in intracellular calcium of washed rabbit platelets caused by collagen and thrombin, while WEB 2086, WEB 2170 and BN 52021 did not have an effect. Norepinephrine (3 microM) induced a sustained contraction in rat thoracic aorta. Pretreatment with these PAF antagonists (20-100 micrograms/ml) caused inhibition of the aortic contraction in the following order: kadsurenone greater than denudatin B greater than WEB 2086 greater than BN 52021 greater than WEB 2170. In high potassium (60 mM)-induced contraction of rat aorta, kadsurenone and denudatin B caused marked relaxation, while WEB 2086, WEB 2170 and BN 52021 had only a slight effect. It is concluded that WEB 2086, WEB 2170 and BN 52021 are specific PAF antagonists in rabbit platelets, and weak relaxants in rat aorta. Two other PAF antagonists, kadsurenone and denudatin B, may inhibit some aspects of signal transduction, e.g., thromboxane formation or intracellular Ca2+ mobilization in rabbit platelets, and cause vasorelaxation in rat aorta by inhibiting calcium influx.

Animals↗
PubMed1991

Vasodilatory action mechanisms of apigenin isolated from Apium graveolens in rat thoracic aorta.

The effect of apigenin, isolated from Apium graveolens, on the contraction of rat thoracic aorta was studied. Apigenin inhibited the contraction of aortic rings caused by cumulative concentrations of calcium (0.03-3 mM) in high potassium (60 mM) medium, with an IC50 of about 48 microM. After pretreatment it also inhibited norepinephrine (NE, 3 microM)-induced phasic and tonic contraction in a concentration (35-140 microM)-dependent manner with an IC50 of 63 microM. At the plateau of NE-induced tonic contraction, addition of apigenin caused relaxation. This relaxing effect of apigenin was not antagonized by indomethacin (20 microM) or methylene blue (50 microM), and still existed in endothelial denuded rat aorta or in the presence of nifedipine (2-100 microM). Neither cAMP nor cGMP levels were changed by apigenin. Both the formation of inositol monophosphate caused by NE and the phasic contraction induced by caffeine in the Ca(2+)-free solution were unaffected by apigenin. 45Ca2+ influx caused by either NE or K+ was inhibited by apigenin concentration-dependently. It is concluded that apigenin relaxes rat thoracic aorta mainly by suppressing the Ca2+ influx through both voltage- and receptor-operated calcium channels.

Animals↗
PubMed1991

Inhibition of platelet aggregation by some flavonoids.

The inhibitory effects of five flavonoids on the aggregation and secretion of platelets were studied. These flavonoids inhibited markedly platelet aggregation and ATP release of rabbit platelets induced by arachidonic acid or collagen, and slightly those by platelet-activating factor. ADP-induced platelet aggregation was also suppressed by myricetin, fisetin and quercetin. The IC50 on arachidonic acid-induced platelet aggregation was: fisetin, 22 microM; kaempferol, 20 microM; quercetin, 13 microM; morin, 150 microM less than IC50 less than 300 microM. The thromboxane B2 formations were also inhibited by flavonoids in platelets challenged with arachidonic acid. Fisetin, kaempferol, morin and quercetin antagonized the aggregation of washed platelets induced by U46619, a thromboxane A2/prostaglandin endoperoxides mimetic receptor agonist. In human platelet-rich plasma, quercetin prevented the secondary aggregation and blocked ATP release from platelets induced by epinephrine or ADP. These results demonstrate that the major antiplatelet effect of flavonoids tested may be due to both the inhibition of thromboxane formation and thromboxane receptor antagonism.

Adenosine Triphosphate↗
PubMed1991

Vasorelaxation of rat thoracic aorta caused by norathyriol isolated from Gentianaceae.

The pharmacological effects of norathyriol on isolated rat thoracic aorta were examined. In the high-K+ (60 mM) medium, Ca2+ (0.03 to 3 mM)-induced vasocontraction was inhibited concentration dependently by norathyriol. Given as pretreatment norathyriol (20 to 200 microM) also inhibited the norepinephrine (NE, 3 microM)-induced tonic contraction. However, the phasic contraction was inhibited only by high concentrations of norathyriol (200 and 400 microM). The tonic contraction elicited by NE was also relaxed by the addition of norathyriol. This relaxing effect of norathyriol was not antagonized by methylene blue (50 microM) or indomethacin (20 microM) and was still seen in denuded rat aorta. Although the cAMP level was not changed by norathyriol, the cGMP level was increased by a high concentration of norathyriol (400 microM). [3H]Inositol monophosphate formation caused by NE was not affected by norathyriol at concentration of either 100 or 400 microM. The 45Ca2+ influx caused by either NE or high K+ was inhibited by norathyriol in a concentration-dependent manner. It is concluded that norathyriol relaxed the rat thoracic aorta mainly by suppressing the Ca2+ influx through both voltage-dependent and receptor-operated calcium channels.

Animals↗
PubMed1991

Dicentrine, a natural vascular alpha 1-adrenoceptor antagonist, isolated from Lindera megaphylla.

1. The pharmacological activity of dicentrine, isolated from Lindera megaphylla, was determined in rat isolated thoracic aorta, guinea-pig isolated trachea and human platelet-rich plasma. 2. Dicentrine was found to be a potent alpha 1-adrenoceptor blocking agent in rat thoracic aorta as revealed by its competitive antagonism of noradrenaline- (pA2 = 8.19 +/- 0.09) or phenylephrine (pA2 = 9.01 +/- 0.10)-induced vasoconstriction. These effects still persisted in denuded aorta. It was less potent than prazosin (pA2 = 10.60 +/- 0.10), but was more potent than phentolamine (pA2 = 7.53 +/- 0.10) or yohimbine (pA2 = 6.20 +/- 0.05). 3. Inositol monophosphate formation induced by noradrenaline (3 microM) in rat thoracic aorta was suppressed by dicentrine (3-10 microM) and prazosin (3 microM). 4. A high concentration of dicentrine (30 microM) did not affect the aortic contraction induced by the thromboxane receptor agonist U-46619 (1 microM), angiotensin II (1 microM), high potassium (60 mM) or carbachol (3 microM). 5. Contraction of guinea-pig trachea caused by histamine or carbachol was slightly inhibited by dicentrine (30 microM), while beta-adrenoceptor relaxation to isoprenaline in trachea was not affected. 6. Aggregation in human platelet-rich plasma induced by adrenaline (10 microM) was blocked by yohimbine (5 microM). A high concentration of dicentrine (greater than 30 microM) caused slight inhibition of aggregation, the release reaction and thromboxane formation. Complete blockade was obtained with 150 microM dicentrine. 7. It is concluded that dicentrine is a potent, selective alpha 1-adrenoceptor antagonist in vascular smooth muscle.

Adrenergic alpha-Antagonists↗
PubMed1991

Antihaemostatic and antithrombotic effect of some antiplatelet agents isolated from Chinese herbs.

Five antiplatelet agents have been isolated from Chinese herbs. Apigenin and magnolol are inhibitors of thromboxane synthesis, while osthole, protopine and norathyriol are inhibitiors of phosphoinositide breakdown. Thirty min after intraperitoneal (i.p.) administration of these drugs, tail bleeding time of mice was prolonged markedly in a dose-dependent manner by norathyriol, protopine, osthole and magnolol, but not by apigenin. However, the antiplatelet agents (up to 200 mg kg-1, i.p.) could not prevent acute thromboembolic death in mice. In endotoxin-induced experimental disseminated intravascular coagulation in rats, norathyriol (50-100 mg kg-1, i.p.) prevented the decrease in platelet counts and fibrinogen, and the prolongation of plasma prothrombin time. Norathyriol (100 mg kg-1, i.p.) also suppressed ex-vivo platelet aggregation induced by collagen and ADP in rat plasma.

Animals↗
PubMed1990

Antiplatelet effects of chelerythrine chloride isolated from Zanthoxylum simulans.

Chelerythrine chloride is an antiplatelet agent isolated from Zanthoxylum simulans. Aggregation and ATP release of washed rabbit platelets caused by ADP, arachidonic acid, PAF, collagen, ionophore A23187 and thrombin were inhibited by chelerythrine chloride. Less inhibition was observed in platelet-rich plasma. The thromboxane B2 formation of washed platelets caused by arachidonic acid, collagen, ionophore A23187 and thrombin was decreased by chelerythrine chloride. Phosphoinositides breakdown caused by collagen and PAF was completely inhibited by chelerythrine chloride, while that of thrombin was only partially suppressed. Chelerythrine chloride inhibited the intracellular calcium increase caused by arachidonic acid, PAF, collagen and thrombin in quin-2/AM-loaded platelets. The cyclic AMP level of washed platelets did not elevated by chelerythrine chloride. The antiplatelet effect of chelerythrine chloride was not dependent on the incubation time and the aggregability of platelets inhibited by chelerythrine chloride was easily recovered after sedimenting the platelets by centrifugation and then the platelet pellets were resuspended. Chelerythrine chloride did not cause any platelet lysis, since lactate dehydrogenase activity was not found in the supernatant. These data indicate that the inhibitory effect of chelerythrine chloride on rabbit platelet aggregation and release reaction is due to the inhibition on thromboxane formation and phosphoinositides breakdown.

Adenosine Triphosphate↗
PubMed1990

Inhibition of rabbit platelet aggregation by 1,4-naphthoquinones.

The effects of four 1,4-naphthoquinone derivatives on the aggregation of rabbit platelets were examined. All the four 1,4-naphthoquinone derivatives inhibited the platelet aggregation of washed rabbit platelets induced by thrombin (0.1 U/ml) and the IC50 is: 2-chloro-3-methyl-1,4-naphthoquinone (CMN), 5 micrograms/ml; 3-methyl-5,8-dihydroxy-1,4-naphthoquinone, 13 micrograms/ml; 5,8-dihydroxy-1,4-naphthoquinone, 18 micrograms/ml; 3-methyl-1,4-naphthoquinone (vitamin K3), 53 micrograms/ml. CMN was the most potent in inhibiting the aggregation and release reaction induced by ADP, arachidonic acid, PAF, ionophore A23187, collagen and thrombin in a dose-dependent manner in washed platelets, platelet-rich-plasma and whole blood. The thromboxane B2 formation caused by collagen and ionophore A23187 was inhibited by CMN. However, the thromboxane B2 formation by arachidonic acid was markedly increased. The platelet inhibitory effect of CMN could not be antagonized either by raising the concentrations of extracellular Ca++ or by wash out. The phosphoinositides breakdown induced by thrombin was inhibited by CMN. Phospholipids (PE, PC, PI) could slightly antagonize the antiplatelet effect of CMN. It is concluded that the inhibitory effect of CMN on rabbit platelet aggregation may be due to the inhibition of phosphoinositides breakdown caused by the inducers.

Adenosine Diphosphate↗