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Potentiation of ADP‐induced aggregation in human platelet‐rich plasma by 5‐hydroxytryptamine and adrenaline
Author(s) -
Vanags D.M.,
Rodgers S.E.,
Duncan E.M.,
Lloyd J.V.,
Bochner F.
Publication year - 1992
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1992.tb14435.x
Subject(s) - ketanserin , chemistry , long term potentiation , adenosine diphosphate , platelet , aspirin , endogeny , thromboxane a2 , medicine , endocrinology , yohimbine , pharmacology , platelet aggregation , biochemistry , serotonin , 5 ht receptor , receptor , biology , antagonist
1 We have used dose‐response curves to quantitate the potentiation of adenosine 5′‐diphosphate (ADP)‐induced aggregation and thromboxane (TXA 2 ) generation by 5‐hydroxytryptamine (5‐HT) and adrenaline in human citrated platelet‐rich plasma. We have also quantitated the inhibition of these responses by aspirin, ketanserin and yohimbine, singly and in pairs. 2 Ketanserin (5 μ m ) inhibited TXA 2 production and the second wave of platelet aggregation induced by a range of concentrations of ADP alone. This indicates that endogenous 5‐HT, released from the platelet dense granules, contributes significantly to responses induced by ADP. 3 When 5‐HT (10 μ m ) was added before ADP, a lower concentration of ADP was required to cause 50% aggregation and TXA 2 generation. The ratio of ADP concentrations (CR) to cause 50% aggregation in the presence and absence of 5‐HT was 2.1 when only added 5‐HT was considered, and 5.0 when endogenous 5‐HT was also taken into account. 4 Potentiation of ADP‐induced aggregation by 5‐HT also occurred in the presence of aspirin, resulting in a CR of 2.3. As expected, ketanserin inhibited potentiation by 5‐HT in the presence and absence of aspirin. Although aspirin caused substantial inhibition of aggregation induced by ADP and 5‐HT (CR 3.4), further inhibition occurred when ketanserin was also present (CR 6.5). 5 A subthreshold concentration of adrenaline (0.25 μ m ) caused substantial potentiation of ADP‐induced aggregation in the absence (CR 4.0) and presence (CR 2.0) of aspirin. As expected, yohimbine (9 μ m ) inhibited this potentiation. Maximum TXA 2 generation induced by ADP increased from 32.5 to 59.4 pg per 10 6 platelets when adrenaline was present. Aggregation induced by ADP and adrenaline was markedly inhibited by aspirin (CR 5.1) but was further inhibited when yohimbine (9 μ m ) was also present (CR 10.0). 6 Results from this in vitro study show ketanserin and yohimbine have the potential to be used in combination with aspirin as antithrombotic agents in vivo .