Adenosine potentiates the inhibitory effects of calcium channel antagonists on human platelet aggregation induced by thromboxane A2 or U46619

SummaryHot water extracts of Mo-er (1 gm by 15 ml of water), an oriental food (Auricularia auricula), inhibit strongly both human and rat platelet ADP-induced aggregation. HPLC analysis of two varieties of Mo-er, A.auricula and A.polytricha (a black tree fungus), shows that they contain adenosine (Ado), 133 and 154 micrograms per gram of dry fungus, respectively. The inhibition of ADP-induced platelet aggregation by Mo-er extracts and by Ado was compared. Mo-er extracts caused a more rapid onset and a longer duration of inhibition than produced by equivalent amounts of Ado. Furthermore, Mo-er extract treated with adenosine deaminase to degrade the Ado retained the capacity to inhibit platelet aggregation. The inhibitory effects of Mo-er extracts on ADP-induced human platelet aggregation are greatly potentiated by the inhibitors of cyclic AMP phosphodiesterase such as oxagrelate (phthalazinol) and papaverine. The inhibition of platelet aggregation is only partially blocked by 2’,5’-dideoxy-adenosine (DDA), an inhibitor of platelet adenylate cyclase and 5’-deoxy, 5’-methylthioadenosine (MTA), an antagonist of Ado receptors. ADP-induced rat platelet aggregation is strongly inhibited by Mo-er extracts, but not by Ado. This inhibition is not reversed by either DDA or MTA. These findings indicate that Mo-er extracts contain an agent (or agents) in addition to Ado, that blocks platelet aggregation by a mechanism that does not involve the platelet cyclic AMP system.

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Structure elucidation and inhibitory effects on human platelet aggregation of chlorogenic acid from Wrightia tinctoria

Journal of Complementary and Integrative Medicine ◽

10.1515/jcim-2012-0048 ◽

2013 ◽

Vol 10 (1) ◽

Cited By ~ 3

Author(s):

Ripal P. Amin ◽

Naveen Kunaparaju ◽

Sunil Kumar ◽

Tony Taldone ◽

Michael A. Barletta ◽

...

Keyword(s):

Platelet Aggregation ◽

Chlorogenic Acid ◽

Structure Elucidation ◽

Human Platelet ◽

Inhibitory Effects ◽

Human Platelet Aggregation ◽

Wrightia Tinctoria

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Differential inhibition of human platelet aggregation and thromboxane A2 formation by L-arginine in vivo and in vitro

Naunyn-Schmiedeberg s Archives of Pharmacology ◽

10.1007/pl00005148 ◽

1998 ◽

Vol 357 (2) ◽

pp. 143-150 ◽

Cited By ~ 18

Author(s):

S. M. Bode-Böger ◽

Rainer H. Böger ◽

Andrea Galland ◽

Jürgen C. Frölich

Keyword(s):

Platelet Aggregation ◽

Human Platelet ◽

Thromboxane A2 ◽

Differential Inhibition ◽

Human Platelet Aggregation

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Thromboxane A2-Stimulated Human Platelet Aggregation Is Potentiated By Epinephrine Acting VIA Alpha Adrenergic Receptors

10.1055/s-0038-1653296 ◽

1981 ◽

Author(s):

G J Johnson ◽

G H R Rao ◽

J G White

Keyword(s):

Platelet Aggregation ◽

Adrenergic Receptors ◽

Human Platelet ◽

Thromboxane A2 ◽

Human Platelets ◽

Adrenergic Agents ◽

Alpha Adrenergic Receptors ◽

Human Platelet Aggregation ◽

Induced Aggregation

Epinephrine (E) potentiates arachidonate (A)-induced aggregation of human platelets. A-insensitive dog platelets (AIP), that form thromboxane A2 (T) but do not aggregate when stirred with A alone, aggregate when exposed to E + A. Therefore, we studied the effect of E on T-stimu- lated human platelet aggregation. AIP stirred with A formed T which was confirmed by TLC. 1/100 to 1/200 volume of AIP was removed 30 sec. after A, and transferred to gel- filtered, aspirin-incubated human platelets. Recipient platelet aggregation was proportional to the volume of AIP transferred. The addition of the thromboxane synthetase inhibitor, Azo Analog I, abolished the aggregating activity of AIP. Transfer of an aliquot of AIP that was inadequate to aggregate human gel-filtered, aspirin-incubated platelets resulted in irreversible aggregation in the presence of ≥0.5nM E. E potentiated aggregation when added 3 min. before but not 3 min. after aliquot transfer. T-stimulated aggregation was abolished by the T-antagonist, 13 azapro- stenoic acid (APA), but E added after APA and before T restored aggregation. E potentiation of T-stimulated aggregation was abolished by prior exposure to equimolar yohimbine, dihydroergocryptine and phentolamine, agents that bind to alpha2 adrenergic receptors, but not by prazosin an alpha1 antagonist. Higher concentrations of E reversed the inhibitory effects of the alpha2 adrenergic agents. All of these agents in higher concentrations (1-100μM) also blocked aggregation induced by T alone. Therefore T-induced platelet aggregation is potentiated by E, in concentrations attained in vivo, by a mechanism linked to platelet alpha adrenergic receptors. Platelet alpha2 receptors have a close functional relationship to the postulated T receptor. E may initiate platelet aggregation in vivo when T is formed in quantities inadequate to alone induce aggregation.

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Prostaglandin F2α antagonizes thromboxane A2-induced human platelet aggregation

Prostaglandins ◽

10.1016/0090-6980(82)90145-9 ◽

1982 ◽

Vol 24 (2) ◽

pp. 195-206 ◽

Cited By ~ 25

Author(s):

S.C. Hung ◽

N.I. Ghali ◽

D.L. Venton ◽

G.C. Le Breton

Keyword(s):

Platelet Aggregation ◽

Human Platelet ◽

Prostaglandin F2α ◽

Thromboxane A2 ◽

Human Platelet Aggregation

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Macrostachyols A-D, oligostilbenes from Gnetum macrostachyum inhibited in vitro human platelet aggregation

Journal of Herbmed Pharmacology ◽

10.34172/jhp.2021.39 ◽

2021 ◽

Vol 10 (3) ◽

pp. 339-343

Author(s):

Serm Surapinit ◽

Nuttakorn Baisaeng

Keyword(s):

Platelet Aggregation ◽

Human Platelet ◽

Adenosine Diphosphate ◽

Positive Control ◽

Inhibitory Effects ◽

Aggregation Assay ◽

Human Platelet Aggregation ◽

Platelet Aggregation Assay ◽

Inhibitory Activities

Introduction: Gnetum macrostachyum is a known Thai medicinal plant as a source of bioactive oligostilbenes, which possess platelet inhibitory activities. The study aimed to evaluate the in vitro human platelet aggregation inhibitory activities of macrostachyols A-D (compounds 1-4) isolated from the roots of G. macrostachyum. Methods: The in vitro human platelet aggregation assay was assayed with a 96-well microtiter plate format. The well-known aggregating agents were used to investigate the possible mechanism of inhibition, including adenosine diphosphate (ADP), arachidonic acid (AA), thromboxane A2 analog (U-46619), collagen, thrombin, and thrombin receptor-activating peptide-6 (TRAP-6). Results: Compound 1 was more potent than ibuprofen (positive control) on the adenosine diphosphate- induced platelet aggregation assay (P < 0.05). Compound 3 was more potent than 1, 2, and 4 (P < 0.05), but all active oligostilbenes were less potent than the positive control (P < 0.05) on the arachidonic acid-induced platelet aggregation assay. The oligostilbenes 1, 2, 3, and 4 also displayed the inhibitory effects on the U-46619-induced platelet aggregation. The tetrameric stilbenes 1 was the only compound that exhibited inhibitory effects on thrombin-induced platelet aggregation without TRAP-6 mediated platelet aggregation. Conclusion: The findings revealed the inhibitory effects of oligostilbenes on human platelet aggregation through a target-specific experimental design. It suggests that oligostilbenes from this plant might be applied as antiplatelet aggregation agents in platelet hyperreactivity- related diseases.

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TRYPTOPHAN PYROLYSIS PRODUCTS FOUND IN COOKED FOODS INHIBIT HUMAN PLATELET AGGREGATION BY INHIBITING CYCLOOXYGENASE

10.1055/s-0038-1643402 ◽

1987 ◽

Author(s):

S Manabe ◽

H Yanagisawa ◽

S Ishikawa ◽

Y Kitagawa ◽

K Tohyama ◽

...

Keyword(s):

Platelet Aggregation ◽

Cell Function ◽

Human Platelet ◽

Human Platelets ◽

Heterocyclic Amines ◽

Inhibitory Effects ◽

Pyrolysis Products ◽

Human Platelet Aggregation ◽

Leukocyte Aggregation

Humans are exposed to numerous toxic compounds in foods. During the past decade, several carcinogenic heterocyclic amines have been reported to be present in the cooked foods. Recently, we reported that some of the carcinogenic heterocyclic amines isolated from foods were present in human plasma. In order to know the effects of the carcinogens isolated from foods on the cell function, we investigated the effects of the carcinogenic heterocyclic amines including Trp-P-1(3-amino-l,4-dimethyl-5H-pyrido❘4,3-b❘indole) and Trp-P-2(3-amino-1-methyl-5H-pyrido❘4,3-b❘indole) on human platelet aggregation and polymorphonuclear leukocyte aggregation. Only tryptophan pyrolysis products, Trp-P-1 and Trp-P-2, had potent inhibitory effects on human platelet aggregation when platelets were preincubated with the carcinogens for 15 min. Other carcinogenic heterocyclic amines such as glutamic acid pyrolysates (Glu-P-1 and Glu-P-2) and 3H-imidazo ❘4,5-f❘quinoline-2-amines(IQ and MelQ) did show no effect on platelet aggregation even at 100 μM.The autoradiogram demonstrated that Tryptophan pyrolysis products, Trp-P-1 and Trp-P-2, dose-dependently inhibited the formation of HHT,PGD2,PGE2 and TXB2 induced by sodium arachidonate in human platelets labeled with ❘ 14c❘ arachidonic acid. Moreover, Trp-P-1 and Trp-P-2 did not show significant effects on leukocyte aggregation induced by sodium arachidonate (0.75mM) even at lOOnM. It is concluded that Trp-P-1 and Trp-P-2 isolated from cooked foodstuffs have potent inhibitory effects on the cyclo-oxygenase pathway of the platelet. Therefore, human platelet function might be affected with daily foods containing tryptophan pyrolysis products in vivo.

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