Summary
Many studies have demonstrated pharmacologic similarities between platelet and brain 5-HT2 binding sites. Therefore it may be possible to use platelets as a model for the central serotonergic neuron. Accordingly, a previcus report (Kusumi et al. 1991b) about elevated [Ca2+]i after serotonin stimulation in platelets of depressed patients was interpreted as further evidence for enhanced serotonergic sensitivity in depression. However, a very recent study showed an enhanced thrombin-induced platelet Ca2+ response, rather suggesting abnormalities of intracellular Ca2+ regulation in affective disorders. In the present study we have determined 5-HT2-and thrombin-induced Ca2+ responses in platelets and additionally phytohemagglutin (PHA)-induced Ca2+ increase in lymphocytes of medicated depressed patients (8 mono- and 2 bipolar, HRSD>17) and of ten sex- and age-matched controls. The results showed no significant difference in basal calcium levels between the two groups and no significant difference in the Ca2+ response to thrombin although the response was higher in the patients. The Ca2+ increase after serotonin stimulation in depressed patients was significantly (P<0.05) higher than in healthy controls. By contrast, the Ca2+ response to PHA in lymphocytes was significantly decreased in the patients. Our data confirm elevated Ca2+ responses after 5-HT2 receptor activation even in medicated depressed patients. However, Ca2+ responses in lymphocytes were decreased. Together with the observations of an enhanced Ca2+ response in platelets after thrombin stimulation, we speculate that the findings rather suggest alterations of [Ca2]i regulation in depression than specific changes of serotonergic sensitivity.
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References
Affolter H, Erne P, Bürgisser E, Pletscher A (1984) Ca2+ as messenger of 5HT2-receptor stimulation in human blood platelets. Naunyn-Schmiedeberg's Arch Pharmacol 325:337–342
Arora RC, Meltzer HY (1989) Increased serotonin2 (5-HT2) receptor binding as measured by3H-lysergic acid diethylamide (3H-LSD) in the blood platelets of depressed patients. Life Sci 44:725–734
Berridge MJ (1993) Inositoltriphosphate and calcium signalling. Nature 361:315–325
Biegon A, Weizman A, Karp L, Ram A, Tiano S, Wolff M (1987) Serotonin 5-HT2 receptor binding on blood platelets — A peripheral marker for depression? Life sci 41:2485–2492
Boyer WF, Feighner JP (1991) The serotonin hypothesis: necessary but not sufficient. In: Feighner JP, Boyer WF (eds), Perspecives in Psychiatry Vol. 1: Selective Serotonin Re-uptake Inhibitors. Wiley, Chichester, pp 71–80
Boyum A (1968) Separation of leucocytes from blood and bone marrow. Scand J Clin Lab Invest 21 [Suppl 97]:77–89
Cai Z, McCaslin PP (1992) Amitriptyline, desipramine, cyproheptadine and carbamazepine, in concentrations used therapeutically, reduce kainate- and N-methyl-D-aspartate-induced intracellular Ca2+ levels in neuronal culture. Eur J Pharmacol 219: 53–57
Cosyns P, Maes M, Vandewoude M, Stevens WJ, De Clerck LS, Schotte C (1989) Impaired mitogen-induced lymphocyte responses and the hypothalamic-pituitary-adrenal axis in depressive disorders. J Affect Disord 16:41–48
De Clerck F, David JL, Janssen PAJ (1982) Inhibition of 5-hydroxy-tryptamine-induced and-amplified human platelet aggregation by ketanserin (R 41468), a selective 5-HT2-receptor antagonist. Agents Actions 12:388–397
Dubovsky SL, Lee C, Christiano J, Murphy J (1991) Elevated platelet intracellular calcium concentration in bipolar depression. Biol Psychiatry 29:441–450
Dubovsky SL, Murphy J, Thomas M, Rademacher J (1992) Abnormal intracellular calcium ion concentration in platelets and lymphocytes of bipolar patients. Am J Psychiatry 149:118–120
Eckert A, Gann H, Riemann D, Aldenhoff J, Müller WE (1993) Elevated intracellular calcium levels after 5-HT2 receptor stimulation in platelets of depressed patients. Biol Psychiatry, in press
Erne P, Pletscher A (1985) Rapid intracellular release of calcium in human platelets by stimulation of 5-HT2-receptors. Br J Pharmacol 84:545–549
Fraser A, Offord SJ, Lucki I (1988): Regulation of serotonin receptors and responsiveness in the brain. In: Sanders-Bush E (ed), The Serotonin Receptors. Humana Press, New Jersey, pp 319–362
Gardner P (1989) Calcium and T-lymphocyte activation. Cell 59: 15–20
Geany DP, Schächter MJ, Elliot M, Grahame-Smith DG (1984) Characterization of [3H] lysergic acid diethylamide binding to a 5-hydroxytryptamine receptor on human platelet membranes. Eur J Pharmacol 97:87–93
Grynkiewicz G, Poenie M, Tsien RY (1985) A new generation of Ca2+ indicators with greatly improved fluroescence properties. J Biol Chem 260:3440–3450
Hartmann H, Eckert A, Förstl H, Müller WE, Similar age-related changes of free intracellular caclium in lymphocytes and central neurons. Effects of Alzheimer's disease. Eur Arch Psychiat Clin Neurosci, in press (this issue)
Kagaya A, Mikuni M, Kusumi I, Yamamoto H, Takahashi K (1990) Serotonin-induced acute desensitization of serotonin2 receptors in human platelets via a mechanism involving protein kinase C. J Pharmacol Exp Ther 255:305–311
Kronfol Z, House JD (1989) Lymphocyte mitogenesis, immunoglobulin and complement levels in depressed patients and normal controls. Acta Psychiatr Scand 80:142–147
Kusumi I, Koyama T, Yamashita I (1991a) Effect of various factors on serotonin-induced Ca2+ response in human platelets. Life Sci 48:2405–2412
Kusumi I, Koyama T, Yamashita I (1991b) Serotonin-stimulated Ca2+ response is increased in the blood platelets of depressed patients. Biol Psychiatry 30:310–312
Kusumi I, Koyama T, Yamashita I (1992) Thrombin-induced platelet calcium mobilization is enhanced in bipolar disorders. Biol Psychiatry 32:731–734
Michel MC, van Tits LJH, Trenn G, Sykora J, Brodde OE (1992) Dissociation between phytohaemagglutinin-stimulated generation of inositolphosphates and Ca2+ increases in human mononuclear leucocytes. Biochem J 285:137–141
Mikuni M, Kusumi I, Kuroda Y, Mori H, Takahashi K (1991) Increased 5-HT2 receptor function as measured by serotoninstimulated phosphoinositide hydrolysis in platelets of depressed patients. Prog Neuropsychopharmacol Biol Psychiatry 15:49–61
Mikuni M, Kagaya A, Takahashi T, Meltzer HY (1992) Serotonin but not norepinephrine-induced calcium mobilization of platelets is enhanced in affective disorders. Psychopharmacology 106:311–314
Nishio H, Ikegami Y, Nakata Y, Segawa T (1993) Relationships between serotonin induced elevation of intracellular Ca2+ concentration and stimulation of Ca2+ influx in blood platelets. Neurochem Int 22:205–210
Pollock WK, Rink TJ (1986) Thrombin and ionomycin can raise platelet cytosolic Ca2+ to micromolar levels by discharge of internal Ca2+ stores: studies using fura-2. Biochem Biophys Res Commun 139:308–314
Schleifer SJ, Keller SE, Meyerson AT, Raskin MJ, Davis KL, Stein M (1984) Lymphocyte function in major depressive disorders. Arch Gen Psychiatry 41:484–486
Vollmayr B, Aldenhoff JB (1994) Cytosolic free [Ca2+] in single T-lymphocytes from depressed patients and healthy controls. Eur Arch Psychiat Clin Neurosci 243:214–217
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Eckert, A., Gann, H., Riemann, D. et al. Platelet and lymphocyte free intracellular calcium in affective disorders. Eur Arch Psychiatry Clin Nuerosci 243, 235–239 (1994). https://doi.org/10.1007/BF02191580
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DOI: https://doi.org/10.1007/BF02191580