Interrelations of Platelet Aggregation and Secretion

Abstract

A B S T R A C T The mechanism of stimulus-response coupling in human platelets was investigated with a new instrument that simultaneously monitors aggregation and secretion in the same sample of plateletrich plasma. When platelets were stimulated by high concentrations of ADP, secretion began only after aggregation was almost complete. With lower concentrations of ADP or with epinephrine, biphasic aggregation was observed, and secretion began simultaneously with, or slightly after, the second phase of aggregation. When platelets were stimulated with high concentrations of y-thrombin or A23187, secretion and aggregation began essentially together. With very low concentrations of y-thrombin or A23187, biphasic aggregation was observed with secretion paralleling the second phase. At every concentration of collagen, secretion and aggregation appeared to be parallel events. Under every condition where the beginning of secretion lagged behind aggregation, secretion was dependent upon aggregation and was inhibited by indomethacin; this is referred to as aggregation-mediated platelet activation. When secretion began at the same time as aggregation, it also occurred in the absence of aggregation and was not blocked by indomethacin; this is referred to as directly induced platelet activation. These observations are -consistent with a simple model of platelet stimulusresponse coupling that includes two mechanisms for activation; aggregation-mediated activation is inhibited by indomethacin, while direct activation does not depend upon aggregation and is not inhibited by indomethacin. Secretion and second wave aggregation appear to be parallel events, with little evidence for second wave aggregation being a consequence of secretion as usually described.

Platelet desensitization induced by arachidonic acid is not due to cyclo‐oxygenase inactivation and involves the endoperoxide receptor

“…Our present hypothesis is that platelets exposed to AA in the presence ofdazoxiben, which do not form TxA2, are desensitized at the endoperoxide receptor level, thus failing to aggregate when re-exposed to AA, but are not desensitized to TxA2 and thus retain the ability to respond to it during the second phase (Figure 6f). In this scheme, we suggest that the endoperoxides are responsible for platelet aggregation and secretion, whereas TxA2 causes the initial cell-to-cell approximation before secretion-dependent irreversible aggregation is triggered, as reported for the early stages of primary aggregation by ADP (Charo et al, 1977).…”

Ginkgolide C Inhibits Platelet Aggregation in cAMP- and cGMP-Dependent Manner by Activating MMP-9

“…32) Collagen-activated platelets require an adequate concentration of intracellular Ca 2ϩ for aggregation, because the formation of platelet is accompanied by the migration of platelets and their adhesion. However, GC significantly blocked Ca 2ϩ release which seems to be critical to the GC-mediated inhibition of platelet aggregation (Fig.…”

Characterization of an anti‐thrombospondin monoclonal antibody (P8) that inhibits human blood platelet functions

“…Similarly a polyclonal antibody directed against a 23-kDa heparin-binding fragment of bovine thrombospondin was also observed to inhibit platelet secretion [16]. Previous studies have shown that at low thrombin concentrations secretion lagged behind the first phase of aggregation [64]. By inhibiting platelet aggregation P8 may also indirectly affect secretion.…”