Signalling components underlying platelet aggregation to a Ca2+ ionophore and a phorbol ester.

Stafford, M; Atkinson, B; Watson, S; Pears, C

Journal article

Signalling components underlying platelet aggregation to a Ca2+ ionophore and a phorbol ester.

Abstract:: Although it is well established that G(q)- and G(i)-coupled receptors can combine to mediate platelet aggregation, the signalling events underlying the synergy are not fully characterised. This study has used the calcium ionophore, A23187, and phorbol ester, PMA, to investigate this question. We show that aggregation to submaximal but not maximal concentrations of ionophore is partially inhibited by antagonism of the P2Y(12) ADP receptor or PKC blockade. However, a full aggregation response can be restored under these conditions by addition of PMA or ADP. Studies using PI 3-kinase inhibitors demonstrate that this is the second messenger pathway that restores aggregation by the G(i)-coupled receptor in the presence of PKC blockade. However, under normal circumstances, PI 3-kinase activity is not a major requirement for aggregation to the ionophore. PMA stimulates a weak aggregation which takes several minutes to reach a maximum. Threshold concentrations of PMA and a G(i)-coupled receptor agonist when added alone show no effect on aggregation, but when combined induce aggregation responses. This study demonstrates that calcium and PKC interact synergistically with a G(i)-coupled receptor agonist to mediate aggregation, and also with each other. Activation of G(i) supports aggregation in part through the PI 3-kinase pathway. High concentration of ionophore on their own can induce aggregation independent of PKC and activation of G(i). Multiple signalling pathways mediate platelet aggregation and their relative importance depends on experimental conditions.

Publication status:: Published

Actions

Email

Email this record

Send the bibliographic details of this record to your email address.

Your Email
Please enter the email address that the record information will be sent to.

-
Your message (optional)
Please add any additional information to be included within the email.
Cite

Cite this record

APA Style

Stafford, M., Atkinson, B., Watson, S., & Pears, C. (2001). Signalling components underlying platelet aggregation to a Ca2+ ionophore and a phorbol ester. Platelets, 12(8), 476–485.

MLA Style

Stafford, M., et al. “Signalling Components Underlying Platelet Aggregation to a Ca2+ Ionophore and a Phorbol Ester.” Platelets, vol. 12, no. 8, 2001, pp. 476–85.

Chicago Style

Stafford, M, B Atkinson, S Watson, and C Pears. 2001. “Signalling Components Underlying Platelet Aggregation to a Ca2+ Ionophore and a Phorbol Ester.” Platelets 12 (8): 476–85.
Share
Print