Plasma Free 5HT and Platelet 5HT in Depression: Case-Control Studies and the Effect of Antidepressant Therapy
In recent years, a number of laboratories have reported on the existence of a non-platelet pool of 5HT in human blood, in the low nM concentration range (Artigas et al., 1985; Anderson et al., 1987). The physiological and pharmacological aspects of the platelet 5HT pool have been extensively studied but little is known about the free 5HT pool in blood. The 5HT found in human platelet-free-plasma (PFP) is thought to be representative of the actual concentration of free 5HT in blood. Results from this laboratory showed that 5HT in PFP and platelet 5HT behave separately after several pharmacological treatments, which provides evidence that 5HT in PFP does not derive ar-tifactually from platelets. In particular, chronic treatment with clomipra-mine — a 5HT uptake inhibitor — elicits a drastic decrease of platelet 5HT (−90% of pre-treatment values) without affecting PFP 5HT (Sarrias et al., 1987). Furthermore, platelet 5HT does not experience marked seasonal changes (± 20%), while plasma 5HT exhibits a 6-fold variation throughout the year in man (Sarrias et al., 1989) and in a large number of healthy people of both sexes. Both are poorly correlated (Ortiz et al., 1988). All these data strongly suggest that most 5HT found in PFP is representative of the actual free 5HT in blood, provided that adequate precautions are taken during blood sampling and treatment. The 5HT in the bloodstream mainly originates in the enterochromaffin cells (E.C.) of the gut, from which it is secreted to either the portal circulation or the gut lumen in response to a variety of different stimuli (Ahlman and Dahlström, 1983; Schwörer et al., 1987). Two mechanisms inactivate the freely circulating 5HT which has strong vasoactive properties (for a review, see Vanhoutte, 1985): uptake (into endothelial cells and platelets) and MAO-A deamination, yielding 5-hydroxyindoleacetic acid (5HIAA). Accordingly, the balance between 5HIAA and 5HT in plasma should be influenced by treatments with MAO inhibitors (MAOI). Also, the ratio between 5HT in platelets and free 5HT in plasma provides a good peripheral index to examine in vivo the effects of drugs affecting 5HT uptake. Both kinds of drugs (MAOI and uptake inhibitors) are effective anti-depressants.
KeywordsUptake Inhibitor Minnesota Multiphasic Personality Inventory Lithium Salt Plasma Serotonin Adequate Precaution
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- Born, G.V.R., Grignani, G., and Martin, L., 1980, Long-term effect of lithium on the uptake of 5-hydroxytryptamine by human platelets, Br. J. Clin. Pharmac., 9: 321–325.Google Scholar
- Poirier, M.F., Galzin, A.M., Pimoule, C., Schoemaker, H., Le Quan Bui, K.H., Meyer, P., Gay, C., Loo, H., and Langer, S.Z., 1988, Short-term lithium administration to healthy volunteers produces long-lasting pronounced changes in platelet serotonin uptake but not imipramine binding, Psycho-pharmacology, 94: 521–526.Google Scholar
- Vanhoutte, P.M., ed., 1985, “Serotonin and the Cardiovascular System”, Raven Press, New York.Google Scholar