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Evidence for an increase in functional platelet 5-HT2A receptors in depressed patients using the new ligand [125I]-DOI

Published online by Cambridge University Press:  16 April 2020

F. Serres ,
J.-M. Azorin ,
M. Valli  and
R. Jeanningros
F. Serres
Affiliation:
Inserm U 501, UER de Médecine Nord, Bd P. Dramard, 13916 Marseilles cedex 20, France
J.-M. Azorin
Affiliation:
Inserm U 501, UER de Médecine Nord, Bd P. Dramard, 13916 Marseilles cedex 20, France
M. Valli
Affiliation:
Inserm U 501, UER de Médecine Nord, Bd P. Dramard, 13916 Marseilles cedex 20, France
R. Jeanningros
Affiliation:
Inserm U 501, UER de Médecine Nord, Bd P. Dramard, 13916 Marseilles cedex 20, France
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Summary

Abnormalities in the serotonergic system have been implicated in the pathophysiology of depressive disorders. Human platelets possess serotonin-2A (5-HT2A) receptors, and previous research using LSD or ketanserin as ligands have indicated that their number is increased in depressed patients. Compared to other ligands previously used in platelet studies, DOI is highly selective for the 5-HT2A receptor and binds to its high-affinity state, therefore labeling only the receptors that are biologically coupled to the G-protein. We determined the density (Bmax) and the affinity (Kd) of 5-HT2A receptors labeled by [125I]-DOI in platelets from 21 untreated patients with major depression and 21 healthy volunteers. The density of the 5-HT2A binding sites was found to be increased in platelets from female depressed patients as compared to controls. No changes were observed in the Kd. We did not find any relationship between the binding parameters and either the severity of the depressive episode or the suicidal tendencies of the patients. Our results show that the number of coupled platelet 5-HT2A receptors is increased in depressed patients, indicating that platelet 5-HT2A receptor function is enhanced in depression.

Keywords

5-HT2A receptorsdepressionDOIplateletserotonin
Type
Original article
Information
European Psychiatry , Volume 14 , Issue 8 , December 1999 , pp. 451 - 457
Copyright
Copyright © Éditions scientifiques et médicales Elsevier SAS 1999

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References

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 3rd ed 1987 Washington, DC: American Psychiatric PressGoogle Scholar
Andres, A.H.Rao, M.L.Ostrowitzki, S.Entzian, W.Human brain cortex and platelet serotonin-2 receptor binding properties and their regulation by endogenous serotonin Life Sci 52 1993 313–321CrossRefGoogle Scholar
Arango, V.Ernsberger, P.Marzuk, P.M.Chen, J.S.Tierney, H.Stanley, M. et al. Autoradiographic demonstration of increased serotonin 5-HT2 and β-adrenergic receptor binding sites in the brain of suicide victims Arch Gen Psychiatry 47 1990 1038–1047CrossRefGoogle ScholarPubMed
Arora, R.C.Meltzer, H.Y.Serotonergic measures in the brains of suicide victims: 5HT2 binding sites in the frontal cortex of suicide victims and control subjects Am J Psychiatry 146 1989 730–736Google Scholar
Arora, R.C.Meltzer, H.Y.Increased serotonin-2 (5-HT2) receptor binding as measured by [3H]-lysergic acid diethylamine ([3H]-LSD) in the blood platelets of depressed patients Life Sci 44 1989 725–734CrossRefGoogle Scholar
Asberg, M.Monoamine neurotransmitters in human aggressiveness and violence: a selective review Crim Behav Ment Health 4 1994 303–327CrossRefGoogle Scholar
Battaglia, G.Shannon, M.Titeler, M.Guanyl nucleotide and divalent cation regulation of cortical S2 serotonin receptors J Neurochem 43 1994 1213–1219CrossRefGoogle Scholar
Biegon, A.Weizman, A.Karp, L.Ram, A.Tiano, S.Wolff, M.Serotonin 5-HT2 receptor binding on blood platelets : A peripheral marker for depression? Life Sci 41 1987 2485–2492CrossRefGoogle ScholarPubMed
Biegon, A.Essar, N.Israeli, M.Elizur, A.Bruch, S.Bar-Nathan, A.A.Serotonin 5HT2 receptor binding on blood platelets as a state dependent marker in major affective disorder Psychopharmacology 102 1990 73–75CrossRefGoogle Scholar
Biegon, A.Grinspoon, A.Blumenfeld, B.Bleich, A.Apter, A.Mester, R.Increased serotonin 5-HT2 receptor binding on blood platelet of suicidal men Psychopharmacology 100 1990 165–167CrossRefGoogle ScholarPubMed
Biegon, A.Greuner, N.Age-related changes in serotonin 5HT2 receptors on human blood platelets Psychopharmacology 108 1992 210–212CrossRefGoogle ScholarPubMed
Chatterjee, D.Anderson, G.M.Chakraborty, M.Cohen, D.J.Human platelet dense granules : improved isolation and preliminary characterization of [3H]-serotonin uptake and tetrabenazine displaceable [3H]-ketanserin binding Life Sci 46 1990 1755–1764CrossRefGoogle ScholarPubMed
Conn, P.J.Sanders-Bush, E.Serotonin-stimulated phosphoinositide turnover : mediation by the S2 binding site in rat cerebral cortex but not in subcortical region J Pharmacol Exp Ther 234 1985 195–203Google ScholarPubMed
Cook, E.H. JrFletcher, K.E.Wainwright, M.Marks, N.Yan, S.Leventhal, L.Primary structure of the human platelet serotonin 5-HT2A receptor: Identity with frontal cortex serotonin 5-HT2A receptor J Neurochem 63 1994 465–469CrossRefGoogle Scholar
Cowen, P.J.Charig, E.M.Fraser, S.Elliott, J.M.Platelet 5-HT receptor binding during depressive illness and tricyclic antidepressant treatment J Affect Dis 13 1987 45–50CrossRefGoogle ScholarPubMed
De Chaffoy, D.E.Courcelles, D.Leysen, J.E.De Clerk, F.VanBelle, H.Janssen, P.A.J.Evidence that phospholipid turnover is the signal transducing system coupled to serotonin-S2 receptor sites J Biochem Chem 206 1985 7603–7608Google Scholar
Declerk, F.David, J.L.Janssen, P.A.Inhibition of 5-hydroxytryptamine-induced and amplified-aggregation by ketanserin (R41468), a selective 5-HT2 receptor antagonist Agents Actions 12 1982 388–397Google Scholar
Elliott, J.M.Kent, A.Comparison of [125I]iodolysergic acid diethylamine binding in human frontal cortex and platelet tissue J Neurochem 53 1989 191–196CrossRefGoogle Scholar
Endicott, J.Spitzer, R.L.Use of the research diagnostic criteria and the schedule for affective disorders and schizophrenia to study affective Disorders Am J Psychiatry 136 1979 52–56Google ScholarPubMed
Fink, G.Sumner, B.E.H.Rosie, R.Grace, O.Quinn, J.P.Estrogen control of central neurotransmission: Effect on mood, mental state, and memory Cell Mol Neurobiol 16 1996 325–343CrossRefGoogle ScholarPubMed
Geaney, D.P.Schachter, M.Elliott, J.M.Grahame-Smith, D.G.Characterization of [3H]-lysergic acid diethylamine binding to a 5-hydroxytryptamine receptor on human platelet membranes Eur J Pharmacol 97 1984 87–93CrossRefGoogle Scholar
Glennon, R.A.Seggel, M.Soine, W.H.David, K.H.Lyon, R.A.Titeler, M.[125I]-DOI: an iodinated radioligand that specifically labels the agonist high affinity state of the 5-HT2 receptor J Med Chem 31 1988 5–7CrossRefGoogle Scholar
Grahame-Smith, D.G.Geaney, D.P.Schachter, M.Elliott, J.M.Human platelet 5-hydroxytryptamine receptors: Binding of [3H]-lysergic acid dyethylamide (LSD) Experientia 44 1988 142–145CrossRefGoogle Scholar
Hamilton, M.Development of rating scale for primary depressive illness Br J Soc Clin Psychol 6 1967 278–296CrossRefGoogle ScholarPubMed
Himeno, A.Saavedra, J.M.Human platelet [125I]-DOI binding sites: characterization by in vitro autoradiography Neuropsychopharmacol 3 1990 25–32Google ScholarPubMed
Hrdina, P.D.Demeter, E.Vu, T.B.Sonotyi, P.Palkovits, M.HT uptake sites and 5-HT2 receptors in brain of antidepressant-free suicide victims/depressives: increase in 5HT2 sites in cortex and amygdala Brain Res 614 1993 37–44CrossRefGoogle Scholar
Hrdina, P.D.Bakish, D.Chudzik, J.Ravindran, A.Lapierre, Y.D.Serotonergic markers in platelets of patients with major depression : Upregulation of 5HT2 receptors J Psychiatry Neurosci 20 1995 11–19Google Scholar
Kayaga, A.Mikuni, M.Takahashi, K.Modulation of 5HT2 receptor-mediated intracellular calcium movement in platelets and its function in affective disorders Jpn J Psychiatry Neurol 45 1991 117–118Google Scholar
Kusumi, I.Koyama, T.Yamashita, I.Serotonin-stimulated Ca2+ response is increased in the blood platelets of depressed patients Biol Psychiatry 30 1991 310–312CrossRefGoogle ScholarPubMed
Leysen, J.E.De Chaffoy, D.E.Courcelles, D.De Clerk, F.Niemegers, C.J.E.VanNeuten, J.M.Serotonin receptor binding sites and functional correlates Neuropharmacology 23 1984 1493–1501CrossRefGoogle ScholarPubMed
Leysen, J.E.Gommeren, W.Janssen, A.J.Identification of non-serotonergic [3H]-ketanserin binding sites on human platelets and their role in serotonin release Eur J Pharmacol 206 1991 39–45CrossRefGoogle ScholarPubMed
Mann, J.J.Stanley, M.Mc Bride, P.A.McEwen, B.S.Increased serotonin-2 and β-adrenergic receptor binding in the frontal cortices of suicide victims Arch Gen Psych 43 1986 954–959CrossRefGoogle Scholar
McBride, P.A.Brown, R.P.Demeo, M.Keilp, J.Mieczkowski, T.Mann, J.J.The relationship of platelet 5HT2 receptor indices to major depressive disorder, personality traits, and suicidal behavior Biol Psychiatry 35 1994 295–308CrossRefGoogle Scholar
McClue, S.J.Brazell, C.Stahl, S.M.Hallucinogenic drugs are partial agonists of the human platelet shape change response: a physiological model of the 5-HT2 receptor Biol Psychiatry 26 1989 297–302CrossRefGoogle ScholarPubMed
McKeith, I.G.Marschall, E.F.Ferrier, I.N.Armstrong, M.M.Kennedy, W.N.Perry, R.H.5-HT receptor binding in post-mortem brain from patients with affective disorder J Affect Dis 13 1987 67–74CrossRefGoogle ScholarPubMed
Mikuni, M.Kusumi, I.Kayaga, A.Kuroda, Y.Mori, H.Takajashi, K.Increased 5-HT2 receptor function as measured by serotonin-stimulated phophoinositide hydrolysis in platelets of depressed patients Prog Neuro-Psychopharmacol Biol Psychiat 15 1991 49–51Google Scholar
Munson, M.Rodbard, R.LIGAND: A versatile computerized approach for the characterization of ligand binding systems Anal Biochem 107 1980 220–239CrossRefGoogle ScholarPubMed
Oliva, D.Pocchiari, F.Allievi, L.Rovati, G.E.Nicosia, S.Non-serotonergic [3H]-ketanserin binding sites in human platelets: Characteristics and interaction with calcium antagonists Pharmacol Res 26 1992 187–199CrossRefGoogle ScholarPubMed
Pandey, G.N.Pandey, S.C.Janicak, P.G.Marks, R.C.Davis, J.M.Platelet serotonin-2 receptor binding sites in depression and suicide Biol Psychiatry 28 1990 215–222CrossRefGoogle ScholarPubMed
Pandey, G.N.Pandey, S.C.Dwivedi, Y.Sharma, R.P.Janicak, P.G.Davis, J.M.Platelet serotonin-2A receptors : a potential biological marker for suicidal behavior Am J Psychiatry 152 1995 850–855Google ScholarPubMed
Pandey, S.C.Sharma, R.P.Janicak, P.G.Marks, R.C.Davis, J.M.Pandey, G.N.Platelet serotonin-2 receptors in schizophrenia : effects of illness and neuroleptic treatment Psychiatry Res 48 1993 57–68CrossRefGoogle ScholarPubMed
Peterson, G.L.A simplification of the protein assay method of Lowry et al which is more generally applicable Anal Biochem. 83 1977 346–348CrossRefGoogle Scholar
Pierce, P.A.Peroutka, S.J.Ring-substituted amphetamine interactions with neurotransmitters receptor binding sites in human cortex Neurosci Lett 95 1988 208–212CrossRefGoogle ScholarPubMed
Steckler, T.Ruggeberg-Schmidt, K.Muller-Oerlinghausen, B.Human platelet 5-HT2 receptor binding sites reevaluated : a criticism of recurrent techniques J Neural Transm Gen Sect 92 1993 11–24CrossRefGoogle Scholar
Teitler, M.Leonhardt, S.Weisberg, E.L.Hoffman, B.J.[125I]iodo-92, 5-dimethoxy) phenylisopropylamine and [3H]-ketanserin labelling of 5-hydroxytryptamine 2 (5HT2) receptors in mammalian cells transfected with a rat cDNA: evidence for multiple state and not for multiple 5HT2 receptor subtypes Mol Pharmacol 38 1990 594–598Google Scholar
Yates, M.Leake, A.Candy, J.M.Fairbain, A.F.McKeith, I.G.Ferrier, I.N.5-HT2 receptor changes in major depression Biol Psychiatry 27 1990 489–496CrossRefGoogle Scholar
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