Platelet aggregation: Part I Some effects of the adenosine phosphates, thrombin, and cocaine upon platelet adhesiveness

Abstract

SYNOPSIS Platelets in native blood adhere spontaneously to glass independently of temperature: if adenosine diphosphate is added to the blood the adhesiveness of the platelets is increased and this effect is largely independent of temperature. The mono-and triphosphates decrease adhesiveness at 20°C. and 37°C. but have no effect at 0°C.; cocaine inhibits adhesion at 37°C. and at 0°C.Aggregation and viscous metamorphosis of platelets in native plasma is induced at 37°C. by adenosine diphosphate or by thrombin; these reactions do not occur at 0°C. Cocaine and all the other anti-adhesive drugs inhibit thrombin or adenosine diphosphate-induced aggregation. The mono-and tri-phosphates appear to compete with adenosine diphosphate and inhibit aggregation; they also inhibit thrombin-induced aggregation. Aggregation induced by adenosine diphosphate or thrombin is not prevented by any of the usual enzyme inhibitors or uncoupling agents at the appropriate strength. At 37°C. aggregation and viscous metamorphosis induced by adenosine diphosphate or thrombin are reversible, and the addition of more adenosine diphosphate or of thrombin again produces aggregation and viscous metamorphosis.Platelets incubated with adenosine diphosphate but not agitated lose their power to aggregate but when more adenosine diphosphate is added with agitation, then aggregation is again produced. These observations are presumably explained by the finding that intact platelets, but not fragmented platelets, can inactivate adenosine diphosphate. From these results it is tentatively concluded that adhesion may involve intrinsic adenosine diphosphate in the platelet which may be activated by thrombin and inhibited by the added mono-or triphosphate. The anti-adhesive drugs act in a different manner. These phenomena have a remarkable similarity to those concerning mitochondrial swelling.It is not known why a platelet sticks, but Hellem (1960) reported that a factor R isolated from red cells caused platelets to stick to glass; 0llgaard (1961) also studied a non-protein extract from platelets and red cells that caused platelet aggregation. Gaarder, Jonsen, Laland, Hellem, and Owren (1961) showed that their factor is adenosine diphosphate, that it is highly specific, and that it induces platelet aggregation in citrated platelet-rich plasma. O'Brien (1961) showed that the adhesion of native platelets to glass and to damaged cells in vitro and in vivo was inhibited by many anti-malarial, anti-histaminic and local anaesthetic and some other drugs which will be called the 'anti-adhesive' drugs. These findings stimulated the present study of the Received for publication 5 February 1962. effects of adenosine diphosphate and thrombin on platelet adhesiveness to glass and on platelet aggregation and viscous metamorphosis. The effect of the anti-adhesive drugs and adenosine monophosphate and the triphosphate and enzyme inhibitors were also studied in an attempt to understand the processes involved in adhesion, aggregation, and viscous metamorphosis.

E. col/ ENDOTOXIN SHOCK IN THE DOG; TREATMENT WITH LIDOCAINE OR INDOMETHACIN

“…A lidocaine concentration of 50 jM inhibits a major prostaglandin degrading enzyme, 15-hydroxy prostaglandin dehydrogenase (Tai & Hollander, 1976). Platelet aggregation and adhesion are inhibited by local anaesthetics which prevent the release of the internal pool of Ca2 + (Feinstein, Fiekers & Fraser, 1976) and compete for the calcium binding sites on the platelet surface (O'Brien, 1962).…”

Evidence for a Structural Requirement for the Aggregation of Platelets by Collagen

“…Platelet-rich plasma (PRP) 1 was prepared from normal subjects by a two-syringe technique with plastic disposable syringes and tlhin-walled 19- The interaction of collagen with platelets was assayed by the technique of platelet aggregation (24,25). The change in optical density of stirred PRP induced by platelet aggregation was measured at 37°C in a platelet aggregometer (Chrono-Log Corp., Broomall, Pa.) with a 609-nm red filter.…”

Stress Induced Platelet Dysfunction in Rats with Folic Acid-Deficient Hyperhomocysteinemia

“…Функциональное состояние тромбоцитов оценивали по их агрегации в цельной крови [11] и суспензии [12][13][14] на Whole blood Chrono Log агрегометре (USA) с использованием следующих индукторов агрегации: АДФ (Eastman) в конечных концентрациях от 5,0 до 10,0 мкМ; коллагена (Chrono Log Corporation) в конечных концентрациях от 2 мкг/мл до 4 мкг/мл и тромбина в конечных концентрациях от 0,3 до 0,5 Ед/мл. Достоверные различия в амплитуде агрегации и скоро сти ее достижения получены при конечной концентрации АДФ 10 мкМ, коллагена 4 мкг/мл и тромбина 0,5 Ед/мл.…”