A comparison of platelet aggregation produced by seven compounds and a comparison of their inhibitors

Abstract

SYNOPSIS The aggregating effects of adenosine diphosphate, thrombin, 5-hydroxytryptamine, tryptamine, adrenaline and noradrenaline, and tri-ethyl tin have been carefully compared. The first three compounds in some circumstances produce remarkably similar effects although there are important differences. The kinetics of aggregation induced by adrenaline (and noradrenaline) are quite different and the tri-ethyl tin effects are different again. Anti-serotonins specifically inhibit 5-hydroxytryptamine and the anti-adrenaline drug phentolamine specifically inhibits the effects of the catecholamines.Experiments presented suggest but do not prove that aggregation produced by all these compounds is accompanied by the liberation of diphosphate from the platelets and that platelet triphosphate may be converted to diphosphate. How these different compounds all produce this effect is discussed. Either the presence of diphosphate or the action of a triphosphatase might be the immediate cause of aggregation if there is a single final common cause. The anti-adrenaline phentolamine prolongs the bleeding time, so adrenaline or noradrenaline may be involved in platelet phenomena in haemostasis.

Inhibition of Adrenaline‐induced Platelet Aggregation by the Α‐adrenoceptor Blocking Drug Benextramine

“…This difference has also been observed with the irreversible x-adrenoceptor blocking drug, phenoxybenzamine. Phenoxybenzamine was 100 times more potent than phentolamine as a postsynaptic a-adrenoceptor blocking drug in the cat isolated spleen and ten times more potent as a presynaptic x-adrenoceptor blocking drug in the cat spleen (Cubeddu, Barnes, Langer & Weiner, 1974) and the rabbit isolated heart (Starke, Montel & Schumann, 1971;Starke, Montel &--Wagner, 1971) and had a very low potency inhuman platelets (Clayton & Cross, 1963;O'Brien, 1963;1964;Bygdeman & Johnsen, 1969;Jakobs, Saur & Schultz, 1978;Lasch & Jakobs, 1979) or was inactive (Born, Mills & Roberts, 1967;Mills & Roberts, 1967a;Hsu, Knapp & Halushka, 1979). Compared to phentolamine, phenoxybenzamine had a higher affinity for both postsynaptic and presynaptic aadrenoceptors but a much lower affinity for platelet o-adrenoceptors.…”

Effects of adrenaline on human blood platelets

“…MILLS AND G. C. K. ROBERTS 1963) which has also not been described in other species. Synergistic effects occur between different aggregating agents (O'Brien, 1964) and ADP aggregation is potentiated by low concentrations of adrenaline (Ardlie, Glew & Schwartz, 1966). We have investigated the effects of adrenaline on the aggregation of human platelets using the turbidimetric method (Born, 1962).…”

Characterization of Receptors Mediating 5‐hydroxytryptamine‐ and Catecholamine‐induced Platelet Aggregation, Assessed by the Actions of Α‐ and Β‐blockers, Butyrophenones, 5‐ht Antagonists and Chlorpromazine

“…Adrenaline and noradrenaline are known to produce platelet aggregation mediated by a-adrenoceptors (O'Brien, 1964) since phentolamine blocks the response whilst propranolol (f,-adrenoceptor blocker) has no effect (Mills & Roberts, 1967a).…”

“…It is well established that the monoamines 5-hydroxytryptamine (5-HT), noradrenaline (NA) and adrenaline cause platelet aggregation (Mitchell & Sharp, 1964;O'Brien, 1964). Gaddum & Picarelli (1957) showed that the 5-HT receptors of the smooth muscle of the guinea-pig ileum are of two kinds: those blocked by dibenzyline, dihydroergotamine and lysergic acid diethylamide (LSD), the D type receptor and those blocked by atropine, morphine and cocaine, the M type receptor.…”