PAF-induced Platelet Aggregation Research Articles

Synthesis and preliminary pharmacological evaluation of some cytisine derivatives

Thirty-one N-derivatives of cytisine were prepared in order to modify its pharmacological profile and to obtain compounds of potential therapeutic interest either at a peripheral or central level, particularly as nicotinic ligands with improved ability to cross the blood–brain barrier. Actually, with the introduction of different kinds of substituent on the basic nitrogen of cytisine a variety of activities were observed, both in vivo (analgesic, dopamine antagonism, antihypertensive, inhibition of stress-induced ulcers, antiinflammatory, protection from PAF-induced mortality, hypoglycemic) and in vitro (positive cardio–inotropic, β-adrenergic antagonism, α 1- and α 2-antagonism, inhibition of PAF-induced platelet aggregation). Six randomly selected compounds were tested for the ability to recognize a central nicotinic receptor and four of them exhibited K i values in the range 30–163 nM.

Inhibitory effect of andrographolide from Andrographis paniculata on PAF-induced platelet aggregation

Andrographolide, an active principle of the Chinese drug Andrographis paniculata, used for prevention and treatment of common cold in Scandinavia and known as an antiinflammatory, antiviral, antithrombotic, hypotensive and antiatherosclerotic drug, was investigated for its suggested influence on the biosynthesis of eicosanoids and the platelet-activating factor (PAF). Whereas in isolated human polymorph-nuclear leukocytes (PMNL) no influence on the biosynthesis was found, it could be shown that andrographolide inhibits PAF-induced human blood platelet aggregation in a dose dependent manner (IC50-5 microM). These results indicate that andrographolide has a mechanism of action different from that of non-steroidal antiinflammatory drugs (NSAID) and most likely associated with the cardiovascular and antithrombotic activity described of Andrographis paniculata.

Effects of chroman derivatives on platelet aggregation induced by some aggregating agents in rabbits.

1. We synthesized 10 chroman derivatives (CD-1 to CD-10) derived from khellactone, including praeruptorin A and praeruptorin B and examined the effects of these compounds on rabbit platelet aggregation. 2. These compounds exhibited an inhibitory effect on platelet-activating factor (PAF)-induced platelet aggregation and their effects were more potent on PAF-induced platelet aggregation than on adenosine triphosphate (ADP)-, arachidonate (AA)- or collagen-induced platelet aggregation. In particular, (+/-)-cis-5-methoxy-6-methoxycarbonyl-2,2-dimethyl-3,4-ditiglyloxychr oman (CD-6), (+/-)-cis-5-methoxy-6-(2-methoxycarbonylethenyl)-2,2-dimethyl- 3,4-ditiglyloxychroman (CD-8), (+/-)-cis-3,4-diacetoxy-5-methoxy-2,2-dimethyl-6-propylchroman (CD-9) and (+/-)-cis-5-methoxy-2,2-dimethyl-6-propyl-3,4-ditiglyloxychroman (CD-10) showed a moderate inhibition of PAF-induced platelet aggregation. 3. From these findings, it is suggested that compounds with potent PAF antagonist activities have the following features: (i) a tiglyloxy moiety is required at the 3 and 4 positions; and (ii) the methoxy moiety is also required at the 5 position of chroman skeleton in khellactone.

A Platelet-Activating Factor Antagonist (WEB 2170) Preserves Endothelium-Dependent Vasodilatation and Prevents Development of a Neo-Intima Induced by a Periarterial Collar in Rabbit Carotid Arteries

Platelet-activating factor (PAF) may be involved in adhesion of leucocytes and migration of cells during vascular remodelling for it is expressed in leucocytes after cytokine priming and is required for cell adhesion. We studied the effects of WEB 2170, a potent PAF antagonist, on the development of an atheroma-like neo-intima induced by a peri-arterial collar in rabbits. Either WEB 2170 (3 mg/kg/day) or vehicle was given by subcutaneous injection once a day for 4 or 9 days, and on day 3 peri-arterial collars were applied to both carotid arteries in all animals. Two or 7 days after implanting the collars vasodilator responses to the endothelium-dependent vasodilator, acetylcholine and the endothelium-independent vasodilator, sodium nitroprusside were studied in isolated artery rings from both groups of rabbits. Neo-intima formation after 7 days (day 10 of treatment) was measured by light microscopy as the ratio of cross-sectional areas of intima and media, and expression of inducible nitric oxide synthase (iNOS) was studied by immunohistochemistry. PAF-induced platelet aggregation ex vivo was inhibited specifically in WEB 2170-treated rabbits. At day 5, acetylcholine-induced vasorelaxation in collared artery rings was markedly impaired as compared to control sections from both vehicle- and WEB 2170-treated rabbits. At day 10, acetylcholine-induced vasorelaxation in collared artery rings from vehicle rabbits was markedly less than in controls, but in WEB 2170-treated rabbits, the acetylcholine response in collared arteries was similar to control sections. Intimal thickening was much reduced in WEB 2170-treated rabbits, ratios of intima/media areas being vehicle: 0.21 ± 0.02 (n = 5) and WEB 2170: 0.07 ± 0.01 (n = 7; p < 0.01). Immunofluorescence showed expression of iNOS only in the neo-intima of vehicle-treated, collared arteries, but not in the residual neo-intima of WEB 2170-treated, collared arteries. These results suggest that WEB 2170 is effective in preserving endothelial function, prevents the development of neo-intima and blocks iNOS expression in the neo-intima in this model.

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.

Pharmacological evidence for the putative existence of two different subtypes of PAF receptors on platelets and leukocytes; studies with yangambin

Yangambin, a new naturally-occuring platelet activating receptor (PAF) receptor antagonist competitively displaced [ 3H]-PAF from its high affinity binding sites on washed human platelets with a Ki value of 1.1 ± 0.3 μM ( n = 3). Studies carried out in parallel demonstrated that SR 27417, a newly-developed PAF receptor antagonist also antagonized [ 3H]-PAF binding to these cells with a Ki value of 51 ± 2 pM. SR 27 417 ( N-(2-dimethylamino ethyl)- N-(3-pyridinyl methyl) [4-(2,4,6-triisopropyl phenyl) thiazol-2-yl] amine) selectively and competitively inhibited the specific binding of [ 3H]-PAF on human polymorphonuclear leukocytes (Ki = 65 ± 5.2 pM) whereas high doses of yangambin remained ineffective. Yangambin inhibited PAF-induced aggregation of human platelets in vitro (IC 50 = 1.0 ± 0.2 μM) but had no effect PAF-induced oxidative burst in human polymorphonuclear leukocytes. In guinea pigs, yangambin inhibited PAF-induced thrombocytopenia but did not affect leukocytopenia whereas SR 27 417 afforded complete protection against both PAF-induced thrombocytopenia and leukocytopenia. In conclusion, yangambin discriminates between two different types of PAF receptors on platelets and polymorphonuclear leukocytes and can be considered as the first PAF receptor antagonist described to date exhibiting such an effect.

Piperbetol, methylpiperbetol, piperol A and piperol B: a new series of highly specific PAF receptor antagonists from Piper betle.

Piperbetol, methylpiperbetol, piperol A, and piperol B, isolated from Piper betle, selectively inhibited the washed rabbit platelet aggregation induced by platelet activating factor (PAF) in a concentration-dependent manner. The IC50 values of piperbetol, methylpiperbetol, piperol A, piperol B, and ginkgolide B were about 18.2, 10.6, 114.2, 11.8, and 4.8 mumol/l, respectively. The inhibitory potency of ginkgolide B was about 2.8, 1.2, 22.8, and 1.4 times higher than those of piperbetol, methylpiperbetol, piperol A, and piperol B. The concentration-response curve of PAF-induced platelet aggregation was shifted to the right by 50 mumol/l of piperbetol, methylpiperbetol, piperol A, piperol B, and ginkgolide B. The EC50 of PAF was increased by these compounds from 1.5 nmol/l to 14.3, 23.1, 2.4, 20.6, and 47.2 nmol/l, respectively. The compounds also inhibited the binding of [3H]-PAF to washed rabbit platelets with IC50 values of 8.7, 5.3, 88, 6.2, and 1.8 mumol/l. Correlating with the inhibitory potency for platelet aggregation, the inhibitory potency of ginkgolide B for binding of PAF was about 3.8, 1.9, 48, and 2.4 times higher than those of piperbetol, methylpiperbetol, piperol A, and piperol B. However, the aggregation of washed rabbit platelets induced by threshold ADP and arachidonic acid were unaffected by piperbetol, methylpiperbetol, piperol A, and piperol B. Furthermore, piperbetol, methylpiperbetol, piperol A, and piperol B had no effects on the cAMP contents in rest washed rabbit platelets. In conclusion, these data indicate that piperbetol, methylpiperbetol, piperol A, and piperol B are effective PAF receptor antagonists in vitro.

Coordination of copper with aspirin enhances its anti-platelet aggregation activity

Anti-platelet aggregation of copper aspirinate, a copper complex of aspirin, has been studied in vitro and in vivo. The result shows that copper aspirinate is much more effective than aspirin against AA-, ADP- and PAF-induced platelet aggregation. Its mechanism is related to the inhibition of platelet cyclooxygenase and release of active substances from platelets, and to the promotion of PGI(2) level in plasma.

Combined effect of Web 2086 (Paf antagonist) and ketoprofen (Nsaid) on Paf-induced ex vivo platelet aggregation in bovine.

The effect of the specific PAF-antagonist WEB 2086, a thieno-triazolo-diazepine, and ketoprofen, a NSAID, was investigated on PAF-induced bovine platelet aggregation measured ex vivo in platelet-rich plasma (PRP). WEB 2086 was infused intravenously over 1 min followed immediately by ketoprofen administration over 1 s (both drugs = 3 mg/kg), in a group of six healthy male Friesian calves. Depending on the PAF concentration, a reversible (10(-8)-10(-9) mol/l) and irreversible (10(-5)-10(-7) mol/l) platelet aggregation was observed. The reversible aggregation was completely blocked by pretreatment of the animal with WEB 2086 and ketoprofen. The inhibitory effects observed during the irreversible aggregation were 47.22%, 54.00% and 88.00% at 10(-5), 10(-6) and 10(-7) mol/l PAF, respectively. Moreover, the aggregation obtained in these condition became reversible. Maximal inhibitory effect of WEB 2086 and ketoprofen on PAF-induced platelet aggregation in calves was observed within 30 min after administration of both drugs. This inhibition persisted even after 24 h and was significantly different from control with P < 0.05. The combined effect of both drugs exceeded the sum of the individual effects (synergism). It was concluded that WEB 2086 and ketoprofen very effectively blocked PAF-induced bovine platelet aggregation in platelet-rich plasma. The study also suggested a synergism between both substances.

Synthesis of substituted cinnamoyl-tyramine derivatives and their platelet anti-aggregatory activities

Substituted cinnamoyl-tyramine derivatives were synthesized by DCC-coupling of substituted cinnamic acid with tyramine or tyramine methyl-1-ether to evaluate PAF-receptor binding antagonistic activities and inhibitory activities on PAF-induced platelet aggregation with interest on structure-activity relations. The results show that 3,4-dimethoxy-cinnamoyl tyramine-amide or its methyl ether have significant PAF-receptor binding antagonistic activity and platelet anti-aggregatory activities.

The effect of intravenous administration of WEB 2086 on PAF-induced platelet aggregation in healthy Friesian calves.

The in vivo ability of the specific PAF-antagonist WEB 2086, a thienotriazolodiazepine, to inhibit platelet-activating factor (PAF) in cattle was investigated by in vitro determination of platelet aggregation curves. WEB 2086 was infused intravenously into a group of 5 healthy male Friesian calves in a dose of 3 mg/kg over 1 min. The resultant inhibition peaked between 30 min and 1 h after administration of WEB 2086. The inhibition was significantly reduced after 3 h and became non-significant after 6 h, but maximal pre-treatment aggregation had not been restored by 24 h after the injection of WEB 2086. These results confirm previous results obtained in vitro and suggest that WEB 2086 is a potent antagonist of PAF activity in calves. They also suggest that further clinical studies with WEB 2086 in cattle are desirable.

Design and modeling of new platelet-activating factor antagonists. 2. Synthesis and biological activity of 1,4-bis-(3′,4′,5′-trimethoxybenzoyl)-2-alkyl and 2-alkyloxymethylpiperazines

In the continuation of our investigations on the structure of platelet-activating factor (PAF)-receptor, 25 additional 2-substituted 1,4-bis-(poly- and mono methoxybenzoyl)-piperazines were synthesized and their in vitro biological activities measured. Substituent at position 2 is representative of the classical balance lipophilicity/hydrophilicity, i.e. alkyl, phenylalkyl, alkoxy and polyalkoxy groups. A potent PAF-induced platelet aggregation inhibitory activity measured in PRP medium is obtained with 5c, IC 50 = 6 × 10 −8 M, which displaces the [ 3H]PAF from platelet membrane with an EC 50 = 6 × 10 −8 M, and compound 4 presents an EC 50 of 3 × 10 −8 M. Examination of structure-activity relationships shows that molecules bearing a hydrophilic or slightly hydrophobic appendix in position-2 are still potent; their IC 50 being included between 10 −6 and 10 −7 M. After quantitative analysis, it seems that in PRP medium, the role of serum albumin must be taken into account instead of a pure hydrophobic interaction of the appendix Z into the receptor. The role of the methoxy groups in producing a potent antagonistic activity is demonstrated by syntheses of several 2-octylpiperazine analogs. These specific features will be quatitatively analysed in the following related publication (part 3).

Exogenous diacylglycerols synergize with PAF with human platelets, but inhibit PAF-induced responses of rabbit platelets

To investigate whether diacylglycerol (DAG) has a role in reversible platelet aggregation induced by low concentrations of platelet-activating factor (PAF), we attempted to use the DAG kinase inhibitor, R59022, to prevent rapid conversion of DAG to phosphatidic acid. However, we found that R59022 inhibited the binding of [ 3H]PAF to human and rabbit platelets and to rabbit platelet membranes. We then investigated whether exogenous, cell-penetrating DAGs (1,2-dihexanoyl- sn-glycerol (DHG) and 1-oleoyl-2-acetyl- sn-glycerol (OAG)) act synergistically with low concentrations of PAF that alone induce only reversible aggregation. Platelets were isolated and labeled with [ 14C]serotonin. DHG (25–75 μM) caused slow, weak aggregation and some release of [ 14C]serotonin with human, but not rabbit, platelets. OAG (25–75 μM) did not aggregate either species' platelets. Phosphorylation of pleckstrin by DHG was more transient in rabbit platelets than previously observed with human platelets. Both DHG and OAG synergistically potentiated PAF-induced aggregation of human platelets, but, paradoxically, concurrently inhibited the PAF-induced increase in intracellular Ca 2+ ([Ca 2+] i); potentiation decreased upon incubation with DAGs before PAF addition. In contrast, DHG strongly inhibited PAF-induced aggregation of rabbit platlets; inhibition decreased upon preincubation. OAG, added with PAF, slightly potentiated aggregation of rabbit platelets; upon preincubation, OAG progressively inhibited. Effects of DHG and OAG on PAF-induced increases in [Ca 2+] i in rabbit platlets followed a similar pattern; thus, with rabbit platelets, inhibition of the [Ca 2+] i increase may at least partially account for inhibition of PAF-induced aggregation by exogenous DAGs. Results with human platelets are consistent with stimulation of protein kinase C by DAGs, and then metabolism of DAGs and/or negative feedback by DAGs, but results with rabbit platelets indicate both an unexpected species difference and a difference between the effects of DHG and OAG on PAF-induced platelet aggregation.

Characterization of [ 3H]apafant binding to PAF receptor on rabbit platelet membranes: A comparison of a Microplate Filtration System and a standard method

This article describes the application of a Microplate Filtration System (MFS) to a binding assay, with the results being compared to those obtained with a conventional 24-Well Filtration Manifold (24WFM). The data reported here characterize the PAF receptor on rabbit platelet membranes using [ 3H]apafant. The results showed that [ 3H]apafant labelled a homogenous population of high-affinity binding sites in a concentration-dependent manner. Binding was very specific, saturable, reversible, and proportional to receptor concentration. [ 3H]Apafant interacted with membranes in an apparently competitive manner, with pseudo-Hill coefficients not significantly different from unity, thus indicating that apafant did not interact cooperatively at these binding sites. A number of PAF antagonists (apafant, lexipafant, BN-52021, SCH-37370, SR-27417, UR-12670) inhibited [ 3H]apafant binding with slopes near unity and with a rank order of potency in good agreement with their ability to inhibit PAF-induced rabbit platelet aggregation, suggesting that the sites labelled are functional PAF receptors. C 18-PAF also competed with [ 3H]apafant for the receptor, but yielded biphasic inhibition curves which could be resolved into high- and low-affinity components. No significant differences were found either in the equilibrium binding parameters or in the PAF antagonists affinities obtained with the 24WFM and the MFS. The use of the latter system improved sample handling efficiency and shortened overall labor time, thus representing a more suitable way to perform receptor binding assays.

Effects of UR-12633, a new antagonist of platelet-activating factor, in rodent models of endotoxic shock.

1. The effects of the selective and potent novel platelet-activating factor (PAF) antagonist, UR-12633 (1-(3,3-diphenylpropionyl)-4-(3-pyridylcyanomethyl)piperidin e) on several markers of endotoxic shock syndrome were evaluated in rats and mice. 2. UR-12633, administered 60 min after E. coli lipopolysaccharide (LPS), reversed the LPS-induced sustained hypotension in rats at doses of 0.01 to 1 mg kg-1, i.v. The reference compound WEB-2086 (1 mg kg-1) also reversed the LPS-induced hypotension. UR-12633 (1 mg kg-1), administered 10 min before LPS, almost fully inhibited sustained hypotension. The immediate hypotension (within 1 min) caused by LPS was not prevented by either UR-12633 or WEB-2086. 3. Pretreatment with 10 mg kg-1, i.v. of either UR-12633 or WEB-2086 inhibited the increase in disseminated intravascular coagulation markers, such as activated partial thromboplastin time (55 and 74% inhibition, respectively), and prothrombin time (22 and 72% inhibition) and prevented the decrease in plasma fibrinogen content (100 and 29% inhibition). 4. Increases in acid phosphatase (ACP) plasma activity, a marker of lysosomal activation, and in lactate dehydrogenase (LDH), a marker of tissue damage, were inhibited by pretreatment with 10 mg kg-1, i.v. of either UR-12633 or WEB-2086 (100% and 69% inhibition, ACP; 62 and 48% inhibition, LDH). Hyperglycaemia (71 and 46%) and hyperlactacidaemia (92 and 56%) were also inhibited. 5. UR-12633, but not WEB-2086, inhibited the LPS-induced increase in vascular permeability in rats, as shown by prevention of haemoconcentration and, to a lesser degree, the increase in Evans blue dye extravasation. 6. In a series of nine reference compounds and UR-12633, we found a high correlation (P < 0.001) between PAF antagonist activity, measured as the inhibition of PAF-induced rabbit platelet aggregation or PAF-induced mortality in mice and the inhibition of LPS-induced mortality. 7. In spite of the multifactorial nature of endotoxic shock, in which many mediators may be involved, the new potent PAF antagonist, UR-12633, proved effective in protecting against changes in most shock markers. These data strongly suggest a key role for PAF in the pathogenesis of endotoxic shock in rodents.

Attenuation of endotoxin-induced pathophysiology by a new potent PAF receptor antagonist.

The role of platelet-activating factor (PAF) as a mediator of endotoxin-induced pathophysiology has been studied in several animal models with conflicting results. We evaluated the effect of a new, potent, and specific PAF receptor antagonist, ABT-299 (Abbott Laboratories) against endotoxin (lipopolysaccharide; LPS)-induced cardiopulmonary dysfunction in a porcine model. In initial experiments, the potency of ABT-299 was confirmed in vitro by its ability to inhibit PAF-induced porcine platelet aggregation at an IC50 of .047 +/- .01 microM, and in vivo by the ability of low doses (.12 mg/kg + .03 mg/kg/h) to block the cardiopulmonary pathologic response to exogenous PAF infusion. To evaluate the effect of ABT-299 administration during endotoxemia, pigs were randomly assigned to one of three groups: controls (n = 7), LPS (n = 9), or ABT-299 + LPS (n =7). ABT-299 was given at 1.0 mg/kg from -0.5 to 0 h plus .3 mg/kg/h from 0 to 6 h. LPS was given at .5 micrograms/kg/hr from 0 to 6 h. ABT-299 reduced the early LPS-induced fall in cardiac index and stroke volume, pulmonary hypertension and vasoconstriction, bronchoconstriction, and hypoxemia. Administration of LPS resulted in 44% mortality (before 6 h), which was blocked by ABT-299. Results with this antagonist indicate that PAF contributes to endotoxin-induced cardiopulmonary dysfunction in the pig, and is associated with mortality in this model.

Platelet aggregation in patients with primary pulmonary hypertension.

Platelet aggregation activity was investigated in patients with primary pulmonary hypertension in different stages of the disease. Platelets were activated with ADP and PAF. Spontaneous platelet aggregation was also measured. Spontaneous and low dose PAF-induced platelet aggregation in patients was greater than in healthy subjects and increased with the severity of the disease. It was concluded that the increased platelet activity can be related to unfavourable prognosis in these patients.

Inhibition of PAF-induced platelet aggregation by WEB 2086 'in-vitro', an antagonist to the receptor for platelet-activating factor, in bovine.

The sensitivity of bovine platelet aggregation in response to PAF stimulation and the ability of WEB 2086 (a thieno-triazolodiazepine) to inhibit response to PAF-induced platelet aggregation were investigated in the blood from five healthy male Belgian Blue calves. The recorded response to PAF showed a plateau which was dependent on the PAF concentration. Platelet aggregation induced by PAF consists of two mechanisms: reversible and irreversible aggregations which are accompanied by the release of platelet granule contents. Reversible aggregation occurred above (2 . 10(-9) mol/l) PAF, and irreversible aggregation occurred above (2 . 10(-7) mol/l) PAF. Addition of WEB 2086 to bovine platelets in vitro induced a rightward shift in the dose-response curve to PAF. WEB 2086 inhibited PAF-induced aggregation in a competitive reversible manner (pA2 = 7.61). The results of our study show that PAF induces platelet aggregation in platelet-rich plasma (PRP) and that addition of WEB 2086 to bovine platelets in vitro inhibits PAF-induced Platelet Aggregation.

The anti-platelet and anti-thrombotic effects of FK633, a peptide-mimetic [formula omitted] antagonist

The anti-platelet and anti-thrombotic properties of FK633, a peptide mimetic GPIIb IIIa antagonist were studied. In human platelet rich plasma, FK633 inhibited ADP-, collagen-, thrombin-, and PAF-induced platelet aggregation with IC50 values of 103, 87, 98, and 239 nM, respectively. RGDS acted similarly, but it's potency was about 1,000 times weaker than FK633. FK633 inhibited 125I-fibrinogen binding to human washed platelet with an IC50 of 88 nM. FK633 did not inhibit α vβ 3, α 5β 1, and α vβ 1 integrin-mediated cellular adhesion up to 1.0mM, while RGDS inhibited all these interactions. In dogs, bolus injection of FK633 at 0.1 mg/kg significantly suppressed ex vivo ADP-induced platelet aggregation (>40% inhibition) and thrombus formation at stenosed and injured coronary artery, but did not prolong template bleeding time. However, FK633 inhibited >90% ADP-induced aggregation at 0.32 mg/kg, causing significant prolongation of the bleeding time. Thus, FK633 is a specific GPIIb IIIa antagonist with potent anti-thrombotic effect in vivo, but careful dosing study might be necessary to avoid the bleeding complications in the clinic.

Effects of taurine on calcium in platelets and their aggregation.

Taurine concentrations are 400-fold greater in platelets than in plasma1, 5. The role of taurine in platelets has not been elucidated. For cardiologists, platelet taurine content is likely to have diagnostic value, since a decrease in taurine concentration in these cells indirectly reflects changes in taurine level in body tissues in general and in heart in particular11. Paasonen et al. 12 have reported that the taurine level in patients with hypertension does not differ from control values but increases in patients with myocardial infarction. In platelets, taurine transport decreases both in hypertension and in cardiovascular failure9. Marked losses of taurine from animals or humans affects the functional state of not only such organs as heart13 and retina8 but also of platelets. Taurine is known to model Ca2+ responses to PAF3. Taurine can inhibit PAF-induced aggregation of guinea pig platelets and aggregation of human platelets induced by ADP, serotonin and epinephrine2. Hayes et al. 9 reported the interrelation of taurine status and platelet aggregation in cat. They discovered that marked loss of taurine from platelets make them more sensitive to aggregation. These authors assume that this effect can be mediated via changes in GSH and altered thromboxane liberation. We suppose that this effect of taurine is not its only platelet action. Taurine may possess a homeostatic action that is revealed in certain pathological conditions. For this reason we have studied taurine effects in cells obtained from donors with different rhythm disturbances.