Characterisation of 2-arachidonylglycerol-induced platelet aggregation in rat whole blood and the influence of gender"leave in review"

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Shearer, J.A. and Kane, K.A. and Coker, S.J. and Carswell, H.V. (2009) Characterisation of 2-arachidonylglycerol-induced platelet aggregation in rat whole blood and the influence of gender"leave in review". pA2 Online: E Journal of the British Pharmacological Society. (Unpublished)

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Abstract

The endocannabinoid, 2-AG, is released from activated platelets and can modulate aggregation in man (Maccarrone et al., 2001). This study aimed to characterise the effects of 2-AG, and its interactions with other agonists, on platelet aggregation in rat whole blood. Male Sprague Dawley rats (300-500g) were anaesthetized with isoflurane and the carotid artery cannulated to allow blood withdrawal. Whole blood aggregometry was used to study the effects of 2-AG, ADP and the interactions among 2-AG, ADP and 5-HT (n=6-7). Data are expressed as mean ± SEM and compared with an unpaired Student’s t-test or a repeated measure 2-way ANOVA (*P<0.05). 2-AG caused slowly developing aggregation that peaked at 10 min in contrast to the response to ADP which peaked at 2 min. Maximal responses to 2-AG 75, 150 and 300 µM were 9.8±3.4, 13.2±0.9 and 14.0±0.7Omega. Aggregation induced by 150 µM 2-AG was reduced to 2.0±1.7*Omega by 1 µM AM251 (CB1 antagonist) and to 0.6±0.5*Omega by 1 µM AM630 (CB2 antagonist). In further experiments, the TP antagonist ICI 192,605 markedly reduced aggregation induced by 150 µM 2-AG from 9.3±2.4 to -0.5±0.1*Omega. 5-HT did not cause platelet aggregation but it potentiated the response to 75 µM 2-AG at 5 min from 5.1±2.8 to 12.4±0.7*Omega. 2-AG prolonged and enhanced the aggregatory response to ADP and this effect was attenuated by ICI 192,605. This study demonstrated that the endocannabinoid, 2-AG, caused platelet aggregation in rat whole blood and interacted with other agonists to modulate aggregation through several mechanisms.

ORCID iDs

Shearer, J.A., Kane, K.A., Coker, S.J. and Carswell, H.V. ORCID logoORCID: https://orcid.org/0000-0002-0938-1212;
CORE (COnnecting REpositories)