Assessment of blood platelets as a model for CNS response: comparative effects of caffeine on 5-HT uptake and release mechanisms in rat platelets and rat brain serotonin neurons.
We have previously reported that caffeine significantly enhanced 5-HT uptake and reduced 5-HT release from crude synaptosomal fractions obtained from rat cerebral cortex and from midbrain raphe region. Blood platelets, as reported by many laboratories and also demonstrated in our own labs, have a very active mechanism for 5-HT uptake and storage. In this regard platelets bear a high degree of similarity to brain serotonin neurons. The present experiments were, therefore, carried out to investigate the effects of caffeine on 5-HT uptake and release from rat platelets in an attempt to assess the possibility of using platelets as a model for studying the CNS effects of caffeine. Platelet rich plasma was prepared from the trunk blood of decapitated rats. Effects of caffeine were investigated at 10(-7), 10(-6), 10(-5) and 10(-4)M, on both the high affinity 3H-5-HT uptake and the spontaneous 5-HT release from 3H-5-HT preloaded platelets. The results show that caffeine did not change 5-HT uptake into platelets. In brain synaptosomes the same concentration of caffeine, however, increased 5-HT uptake dose-dependently. The results also revealed that caffeine increased 5-HT release from rat platelets in a concentration-dependent manner. The concentrations 10(-6), 10(-5), and 10(-4)M increased release significantly compared to control. This finding is also in contrast to that observed in synaptosomes of brain serotonin neurons where caffeine decreased 5-HT release. It is concluded, therefore, that the rat blood platelet is not a suitable model for studying these CNS actions of caffeine. Furthermore, our observations imply that rat platelet serotonin uptake and release mechanisms are not identical to those mechanisms in brain serotonin neurons.
D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002110:Caffeine / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008959:Models, Neurological; D011903:Raphe Nuclei / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000097:blood / Q000378:metabolism*
D012701:Serotonin; D002110:Caffeine