Hostname: page-component-78c5997874-xbtfd Total loading time: 0 Render date: 2024-11-19T19:36:41.850Z Has data issue: false hasContentIssue false
  • English
  • Français

Datos para un aumento en los receptores 5-HT2A funcionales de las plaquetas en pacientes deprimidos utilizando el nuevo ligando [l25I]-DOI

Published online by Cambridge University Press:  12 May 2020

F. Serres ,
J.M. Azorin ,
M. Valli  and
R. Jeanningros
F. Serres
Affiliation:
Inserm U 501, UER de Medicine Nord, BdP. Dramard, 13916Marseilles cedex 20, Francia
J.M. Azorin
Affiliation:
Inserm U 501, UER de Medicine Nord, BdP. Dramard, 13916Marseilles cedex 20, Francia
M. Valli
Affiliation:
Inserm U 501, UER de Medicine Nord, BdP. Dramard, 13916Marseilles cedex 20, Francia
R. Jeanningros
Affiliation:
Inserm U 501, UER de Medicine Nord, BdP. Dramard, 13916Marseilles cedex 20, Francia
Get access

Resumen

Se han implicado anomalías en el sistema serotonérgico en la patofisiología de los trastornos depresivos. Las plaquetas humanas poseen receptores de serotonina-2A (5-HT2A), e investigaciones anteriores que han utilizado LSD o ketanserina como ligandos han indicado que su número se incrementa en los pacientes deprimidos. Comparado con otros ligandos utilizados antes en los estudios de plaquetas, el DOI es muy selectivo para el receptor 5-HT2A y se fija a su estado de alta afinidad, marcando por tanto sólo los receptores que están asociados biológicamente a la proteína G. Determinamos la densidad (Bmax) y la afinidad (Kd) de receptores 5-HT2A marcados por [l25I]-DOI en las plaquetas de 21 pacientes no tratados con depresión mayor y 21 voluntarios sanos. Se encontró que la densidad de los sitios de fijación de 5-HT2A se incrementaba en las plaquetas de las pacientes deprimidas en comparación con los controles. No se observaron cambios en la Kd. No encontramos ninguna relación entre los parámetros de fijación y la gravedad del episodio depresivo o las tendencias suicidas de los pacientes. Nuestros resultados muestran que el número de receptores 5-HT2A acoplados de las plaquetas se incrementa en los pacientes deprimidos, lo que indica que la función del receptor 5-HT2A de las plaquetas aumenta en la depresión.

Keywords

receptores 5-HT2AdepresiónDOIplaquetasserotonina
Type
Artículo original
Information
European Psychiatry (Ed. Española) , Volume 7 , Issue 5 , June 2000 , pp. 294 - 303
Copyright
Copyright © European Psychiatric Association 2000

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Bibliografía

American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 3rd ed.Washington, DC: American Psychiatric Press; 1987.Google Scholar
Andres, AHRao, MLOstrowitzki, SEntzian, W.Human brain cortex and platelet serotonin-2 receptor binding properties and their regulation by endogenous seroto-nin. Life Sci 1993;52:313–21.CrossRefGoogle Scholar
Arango, VErnsberger, PMarzuk, PMChen, JSTierney, HStanley, 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 1990;47:1038–47.CrossRefGoogle ScholarPubMed
Arora, RCMeltzer, HY.Serotonergic measures in the brains of suicide victims: 5-HT2 binding sites in the frontal cortex of suicide victims and control subjects. Am J Psychiatry 1989;146:730–6.Google ScholarPubMed
Arora, RCMeltzer, HY.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 1989;44:725–34.CrossRefGoogle Scholar
Asberg, M.Monoamine neurotransmitters in human aggressiveness and violence: a selective review. Crim Behav Ment Health 1994;4:303–27.CrossRefGoogle Scholar
Battaglia, GShannon, MTiteler, M.Guanyl nucleotide and divalent regulation of cortical S2 serotonin recep-tors. J Neurochem 1994;43:1213–9.CrossRefGoogle Scholar
Biegon, AWeizman, AKarp, LRam, ATiano, SWolff, M.Serotonin 5-HT2 receptor binding on blood platelets: A peripheral marker for depression? Life Sci 1987;41:2485–92.CrossRefGoogle ScholarPubMed
Biegon, AEssar, NIsraeli, MElizur, ABruch, SBar-Nathan, AA.Serotonin 5HT2 receptor binding on blood platelets asa State dependent marker in major affective disorder. Psychopharmacology 1990;102:73–5.CrossRefGoogle Scholar
Biegon, AGrinspoon, ABlumenfeld, BBleich, AApter, AMester, R.Increased serotonin 5-HT2 receptor binding on blood platelet of suicidal men. Psychopharmacology 1990;100:165–7.CrossRefGoogle ScholarPubMed
Biegon, AGreuner, N.Age-related changes in serotonin 5HT2 receptors on human blood platelets. Psychopharmacology 1992;108:210–2.CrossRefGoogle ScholarPubMed
Charterjee, DAnderson, GMChakraborty, MCohen, DJ.Human platelet dense granules: improved isolation and preliminary characterization of [3H]-serotonin uptake and tetrabenazine displaceable [3H]-ketanserin binding. Life Sci 1990;46:1755–64.CrossRefGoogle Scholar
Conn, PJSanders-Bush, E.Serotonin-stimulated phos-phoinosticide turnover: mediation by the S2 binding site in rat cerebral cortex but not ins subcortical region. J Pharmacol Exp Ther 1985;234:195–203.Google ScholarPubMed
Cook EH Jr, Fletcher, KEWainwright, MMarks, NYan, SLeventhal, L.Primary structure of the human platelet serotonin 5-HT2A receptor: Identity with frontal cortex serotonin 5-HT2A receptor. J Neurochem 1994;63:465–9.Google Scholar
Cowen, PJCharig, EMFraser, SElliott, JM.Platelet 5-HT receptor binding during depressive illness and tricyclic antidepressant treatment. J Affect Dis 1987;13:45–50.CrossRefGoogle ScholarPubMed
De Chaffoy, DECourcelles, DLeysen, JEDe Clerk, FVaBelle, HJanssen, PAJ.Evidence that phospholipid turnover is the signal transducing System coupled to sero-tonin-S2 receptor sites. J Biochem Chem 1985;206:7603–8.Google Scholar
Declerk, FDavid, JLJanssen, PA.Inhibition of 5-hydroxytryptamine-induced and amplified-aggregation by ketanserin (R41468), a selective 5-HT2 receptor anta-gonist. Agents Actions 1982;12:388–97.Google Scholar
Elliott, JMKent, A.Comparison of [125I]iodolysergic acid diethylamine binding in human frontal cortex and platelet tissue. J Neurochem 1989;53:191–6.CrossRefGoogle Scholar
Endicott, JSpitzer, RL.Use of the research diagnostic cri-teria and the schedule for affective disorders and schi-zophrenia to study affective Disorders. Am J Psychiatry 1979;136:52–6.Google Scholar
Flink, GSumner, BEHRosie, RGrace, OQuinn, JP.Estrogen control of central neurotransmission: Effect on mood, mental State, and memory. Cell Mol Neurobiol 1996;16:325–43.CrossRefGoogle Scholar
Geaney, DPSchachter, MElliott, JMGrahame-Smith, DG.Characterization of [3H]-lysergic acid diethylamine binding to a 5-hydroxytryptamine receptor on human platelet membranes. Eur J Pharmacol 1984;97:87–93.CrossRefGoogle Scholar
Glennon, RASeggel, MSoine, WHDavid, KHLyon, RATiteler, M.[125I]-DOI: and iodinated radioligand that specifically labels the agonist high affinity State of the 5-HT2 receptor. J Med Chem 1988;31:5–7.CrossRefGoogle Scholar
Grahame-Smith, DGGeaney, DPSchachter, MElliott, JM.Human platelet 5-hydroxytryptamine receptors: Binding of [3H]-lysergic acid dyethylamide (LSD). Experientia 1988;44:142–5.CrossRefGoogle Scholar
Hamilton, M.Development of rating scale for primary depressive illness. Br J Soc Clin Psychol 1967;6:278–96.CrossRefGoogle ScholarPubMed
Himeno, ASaavedra, JM.Human platelet [125I]-DOI bin-ding sites: characterization by in vitro autoradiography. Neuropsychopharmacol 1990;3:25–32.Google Scholar
Hrdina, PDDemeter, EVu, TBSonotyi, PPalkovits, M.HT uptake sites and 5-HT2 receptors in brain of antidepres-sant-free suicide victims/depressives: increase in 5HT2 sites in cortex and amygdala. Brain Res 1993;614:37–44.CrossRefGoogle Scholar
Hrdina, PDBakish, DChudzik, JRavindran, ALapierre, YD.Serotonergic markers in platelets of patients with major depression: Upregulation of 5HT2 receptors. J Psychiatry Neurosci 1995;20:11–19.Google Scholar
Kayaga, AMikuni, MTakahashi, K.Modulation of 5HT2 receptor-mediated intracellular calcium movement in platelets and its function in affective disorders. Jpn J Psychiatry Neurol 1991;45:117–8.Google Scholar
Kusumi, IKoyama, TYamishita, I.Serotonin-stimulated Ca2+ response is increased in the blood platelets of depressed patients. Biol Psychiatry 1991;30:310–2.CrossRefGoogle ScholarPubMed
Leysen, JEDe Chaffoy, DECourcelles, DDe Clerk, FNiemegers, CJEVanNeuten, JM.Serotonin receptor bin-ding sites and functional correlates. Neuropharmacology 1984;23:1493–1501.CrossRefGoogle Scholar
Leysen, JEGommeren, WJanssen, AJ.Identification of non-serotonergic 13H]-ketanserin binding sites on human platelets and their role in serotonin release. Eur J Pharmacol 1991;206:39–45.CrossRefGoogle Scholar
Mann, JJStanley, MMe Bride, PAMcEwen, BS.Increased serotonin-2 and β-adreneigic receptor binding in the frontal cortices of suicide victims. Arch Gen Psych 1986;43:954–9.CrossRefGoogle Scholar
McBride, PABrown, RPDemeo, MKeilp, JMieczkowski, TMann, JJ.The relationship of platelet 5HT2 receptor indices to major depressive disorder, personality traits, and suicidal behavior. Biol Psychiatry 1994;35:295–308.CrossRefGoogle Scholar
McClue, SJBrazell, CStahl, SM.Hallucinogenic drugs are partial agonists of the human platelet shape change response: a physiological model of the 5-HT2 reepetor. Biol Psychiatry 1989;26:297–302.CrossRefGoogle Scholar
McKeith, IGMarschall, EFFerrier, INArmstrong, MMKennedy, WNPerry, RH, et al.5-HT receptor binding in post-mortem brain from patients with affective disorder. J Affect Dis 1987;13:67–74.CrossRefGoogle ScholarPubMed
Mikuni, MKusumi, IKayaga, AKuroda, YMori, HTakajashi, K.Increased 5-HT2 receptor function as mea-sured by serotonin-stimulated phophoinositide hydroly-sis in platelets of depressed patients. Prog Neuro-Psychopharmacol Biol Psychiat 1991;15:49–51.Google Scholar
Munson, MRodbard, R.LIGAND: A versatile computeri-zed approach for the characterization of ligand binding systems. Anal Biochem 1980;107:220–39.CrossRefGoogle ScholarPubMed
Oliva, DPocchiari, FAllievi, LRovati, GENicosia, S.Nonserotonergic [3H]-ketanserin binding sites in human platelets: Characteristics and interaction with calcium antagonists. Pharmacol Res 1992;26:187–99.CrossRefGoogle Scholar
Pandey, GNPandey, SCJanicak, PG,. Marks, RCDavis, JM.Platelet serotonin-2 receptor binding sites in depression and suicide. Biol Psychiatry 1990;28:215–22.CrossRefGoogle ScholarPubMed
Pandey, SCPandey, SCJanicak, PGMarks, RCDavis, JM.Platelet serotonin-2 receptor binding sites in depression and suicide. Biol Psychiatry 1990;28:215–22.CrossRefGoogle ScholarPubMed
Pandey, SCSharma, RPJanicak, PGMarks, RCDavis, JMPandey, GN.Platelet serotonin-2 receptors in schizoph-renia: effeets of illness and neuroleptic treatment. Psychiatry Res 1993;48:57–68.CrossRefGoogle Scholar
Peterson, GL.A simplification of the protein assay met-hod of Lowry et al which is more generally applicable. Anal Biochem. 1977;83:346–8.CrossRefGoogle Scholar
Pierce, PAPeroutka, SJ.Ring-substituted amphetami-ne interactions with neurotransmitters receptor binding sites in human cortex. Neurosci Lett 1988;95:208–12.CrossRefGoogle ScholarPubMed
Steckler, TRuggeberg-Schmidt, KMuller-Oerlinghausen, B.Human platelet 5-HT2 receptor binding sites reeva-luated: a criticism of recurrent techniques. J Neural Transm Gen Sect 1993;92:11–24.CrossRefGoogle Scholar
Teitler, MLeonhardt, SWeisberg, ELHoffman, BJ.[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 1990;38:594–8.Google Scholar
Yates, MLeake, ACandy, JMFaibrain, AFMcKeith, IGFerrier, IN.5-HT2 receptor changes in major depression. Biol Psychiatry 1990;27:489–96.CrossRefGoogle Scholar