Previous work in our lab has demonstrated that platelet Ca2+ signalling is potentiated through a pericellular recycling system, which would appear to require the nanojunction created at the platelet membrane complex (PMC).1 However to further test this hypothesis requires an ability to experimentally manipulate the PMC. Le Menn et al., (1979) demonstrated that a short pre-incubation with nicergoline is able to trigger a reorganisation of both the open canalicular- and dense tubular systems, through its ability to disuprt the cortical microtubules of platelets.2 Experiments were therefore performed to examine whether this drug could inhibit platelet calclum signalling through preventing pericellular calcium recycling. Platelets were isolated from blood obtained by venepuncture of healthy volunteers under informed consent and with local ethical committee approval in accordance with the declaration of Helsinki. Thrombin-evoked changes in cytosolic- [Ca2+]cyt) and pericellular ([Ca2+]peri) Ca2+ concentration were monitored in Fura-2- and FFP-18-loaded platelets, using our previously published methodology. 1 Platelet microtubule structure was monitored in cells co-loaded with 5 µM Fura-red/AM for 45 minutes and 500 nM Tubulin tracker for 30 minutes at 37°C. Data are presented as mean % of control ± SEM of the number of samples (n) indicated. Statistical significance was tested by Student’s t-test. Pretreatment of platelets for 5 minutes at 37°C with 100 µM nicergoline had an inhibitory effect on thrombin-evoked changes in [Ca2+]cyt evoked elicited in the absence of extracellular Ca2+ (64.6% ± 5.1% of control, P<0.05, n=7). However when platelets were pretreated with 100 µM taxol for 30 minutes at 37°C prior to treatment with nicergoline, this drug was not able to elicit any significant effect on thrombin-evoked changes in [Ca2+]cyt (107.2% ± 7.0% of control, P <0.05, n=7). In line with an effect on pericellular Ca2+ recycling, pretreatment with nicergoline abolished the thrombin-evoked rise in [Ca2+]peri. Again prior treatment with the microtubule-stabilising drug taxol, was able to prevent the inhibitory effect of nicergoline on thrombin-evoked rises in [Ca2+]peri. Examination of platelets loaded with tubulin tracker by confocal microscopy demonstrated that pretreatment of platelets with 100 µM nicergoline was able to elicit a disruption of the normal microtubule structure of these cells. These experiments demonstrate that nicergoline is able to disrupt platelet calcium signalling through disruption of the microtubule structure of these cells – further work is ongoing to see whether this relates to a disruption of the PMC.