ADP-induced platelet aggregation and actin polymerization. Involvement of GpIIb/IIIa and the effect of Mg2+.
We have investigated the effects of Mg2+ (added to platelet rich plasma [PRP] as 10mM MgCl2 or MgSO4) on the platelet aggregation and actin polymerization that occurs in response to adenosine diphosphate (ADP). The PRP was prepared from blood containing hirudin as anticoagulant. Mg2+ added before 1 microM ADP completely inhibited aggregation and markedly inhibited actin polymerization. Mg2+ (10mM) added before 10 microM ADP converted irreversible aggregation into a reversible response; similarly, apparently irreversible actin polymerization was converted to a reversible response in which polymerization was followed by some actin depolymerization. Mg2+ added after inducing platelet aggregation with 10 microM ADP produced parallel disaggregation of platelets and actin depolymerization. Actin polymerization occurs immediately on adding ADP to PRP (in association with shape change) and further polymerization occurs in association with platelet aggregation. When aggregation (and the actin polymerization associated with this) was prevented by adding M148, a monoclonal antibody directed at the GpIIb/IIIa complex, or simply by avoiding stirring the sample, Mg2+ had no effect on actin polymerization/depolymerization. Thus Mg2+ only affected the changes in actin that were associated with the aggregation response. This was in contrast to iloprost (which acts at the PGI2 receptor to stimulate adenylate cyclase) which induced rapid actin depolymerization when added after ADP stimulation of platelets under circumstances where platelet aggregation was avoided. These results show that Mg2+ affects actin polymerization as well as platelet aggregation, and that it affects the actin polymerization associated with aggregation but not that associated with shape change (in contrast to iloprost which inhibits both).(ABSTRACT TRUNCATED AT 250 WORDS)
Heptinstall
S
S
Department of Medicine, University Hospital, Queen's Medical Centre, Nottingham, United Kingdom.
Glenn
J R
JR
Lösche
W
W
Spangenberg
P
P
D000199:Actins / Q000737:chemistry*; D000244:Adenosine Diphosphate; D000911:Antibodies, Monoclonal; D001704:Biopolymers; D004359:Drug Therapy, Combination; D006801:Humans; D008274:Magnesium / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects*; D010980:Platelet Membrane Glycoproteins / Q000502:physiology*; D013268:Stimulation, Chemical
D000199:Actins; D000911:Antibodies, Monoclonal; D001704:Biopolymers; D010980:Platelet Membrane Glycoproteins; D000244:Adenosine Diphosphate; D008274:Magnesium