Skip to main content
SpringerLink
Log in

[3H]Ketanserin Binding in Human Brain Postmortem

  • Published:
Neurochemical Research Aims and scope Submit manuscript

Abstract

This study aimed at comparing the binding characteristics of [3H]ketanserin, a high-affinity serotonin 2A (5-HT2A) receptor antagonist, in the prefrontal cortex, hippocampus and striatum of human brain post-mortem. The results indicated the presence of a single population of binding sites in all the regions investigated, with no statistical difference in maximum binding capacity (Bmax) or dissociation constant (Kd) values. The pharmacological profile of [3H]ketanserin binding was consistent with the labeling of the 5-HT2A receptor, since it revealed a competing drug potency ranking of ketanserin = spiperone > clozapine = haloperidol > methysergide > mesulergine > 5-HT. In conclusion, the 5-HT2A receptor, as labeled by [3H]ketanserin, would seem to consist of a homogenous population of binding sites and to be equally distributed in human prefronto-cortical, limbic and extrapyramidal structures.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

REFERENCES

  1. Jacobs, B. L., and Formal, C. A. 1995. Serotonin and behaviour: a general hypothesis. Pages: 461–469, in Bloom, F. E., and Meltzer, H. Y. (eds.), Psychopharmacology: The Fourth Generation of Progress, Raven Press, New York.

    Google Scholar 

  2. Martin, G. R., and Humphrey, P. P. A. 1994. Receptors for 5-hydroxytryptamine: current perspectives on classification and nomenclature. Neuropharmacol. 33:261–273.

    Google Scholar 

  3. Lovenberg, T. W., Erlander, M. G., Baron, B. M., and Sutcliffe, J. G. 1993. Cloning of new 5-HT receptors. Int. Clin. Psychopharmacol. 8(S2):19–23.

    Google Scholar 

  4. De Clerck, F., Xhoneeux B., Leysen, J., and Janssen, P. A. J. 1984. Evidence for functional 5HT2 receptor sites on human blood platelets. Biochem. Pharmacol. 33:2807–2811.

    Google Scholar 

  5. Houston, D. S., and Vanhoutte, P. M. 1988. Comparison of serotonergic receptor subtypes on the smooth muscle and endothelium of the canine coronary artery. J. Pharmacol. Exp. Ther. 244: 1–10.

    Google Scholar 

  6. Arango, V., Ernsberger, P., Marzuk, P. M., Chen, J. S., Tierney, H., Stanley, M., Reis, D. J., and Mann, J. J. 1990. Autoradiographic demonstration of increased serotonin 5HT2 and beta-adrenergic receptor binding sites in the brain of suicide victims. Arch. Gen. Psychiatry 47:1038–1047.

    Google Scholar 

  7. Hrdina, P. D., Demeter, E., Vu, T. B., Sotonyi, P., and Palkovits, M. 1993. 5-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. 614:37–44.

    Google Scholar 

  8. Blumensohn, R., Ratzoni, G., Weizman, A., Israeli, M., Greuner, N., Apter, A., Tyano, S., and Biegon, A. 1995. Reduction in serotonin 5HT2 receptor binding on platelets of delinquent adolescents. Psychopharmacol. 118:354–356.

    Google Scholar 

  9. Glennon, R. A. 1990. Do classical hallucinogens act as 5-HT2 agonist or antagonist? Neuropsychopharmacol. 3:509–517.

    Google Scholar 

  10. Heninger, G. R. 1991. The role of serotonin in clinical disorders. Pages 471–482, in Bloom, F. E., and Meltzer, H. Y. (eds.), Psychopharmacology: The Fourth Generation of Progress, Raven Press, New York.

    Google Scholar 

  11. Gerlach, J. 1991. New antipsychotics: classification, efficacy, and adverse effects. Schiz. Bull. 155(suppl. 5):33–36.

    Google Scholar 

  12. Roth, B. L., Ciaranello, R. D., and Meltzer, H. Y. 1992. Binding of typical and atypical antipsychotic agents with transiently expressed 5-HT1C receptors. J. Pharmacol. Exp. Ther. 260:1361–1365.

    Google Scholar 

  13. Deakin, J. F. W., and Pennel, I. 1989. 5-HTergic receptor subtypes in depression. Psychopharmacol. S24.

  14. Araneda, R., and Andrade, R. 1991. 5-hydroxytryptamine2 and 5-hydroxytryptamine1A receptors mediate opposing responses on membrane excitability in rat association cortex. Neuroscience 40: 399–412.

    Google Scholar 

  15. Schreiber, R., and De Vry, J. 1993. 5-HT1A receptor ligands in animal models of anxiety, impulsivity and depression: multiple mechanisms. Prog. Neuropsychopharmacol. Biol. Psychiatry 17/1: 87–104.

    Google Scholar 

  16. Zifa, E., and Fillion, G. 1994. 5-Hydroxytryptamine receptors. Pharmacol. Rev. Vol. 44(3):402–457.

    Google Scholar 

  17. Pazos, A., Probst, A., and Palacios, J. M. 1987. Serotonin receptors in the human brain. IV. Autoradiographic mapping of serotonin-2 receptors. Neuroscience 21:123–139.

    Google Scholar 

  18. Mengod, G., Pompeiano, M., Martinez-Mir, M. I., and Palacios, J. M. 1990. Localization of the mRNA for the 5HT2 receptor by in situ-hybridization histochemistry. Correlation with the distribution of receptor sites. Brain Res. 524:139–143.

    Google Scholar 

  19. Burnet, P. W. J., Eastwood, S. L., Lacey, K., and Harrison, P. J. 1995. The distribution of 5-HT1A and 5-HT2A receptor mRNA in human brain, Brain Res. 676:157–168.

    Google Scholar 

  20. Pasqualetti, M., Nardi, I., Ladinsky, H., Marazziti, D., and Cassano, G. B. 1996. Comparative anatomical distribution of serotonin 1A, 1Da and 2A receptor mRNAs in human brain postmortem. Mol. Brain Res. 39:223–233.

    Google Scholar 

  21. Hoyer, D., Pazos, A., Probst, A., and Palacios, J. M. 1986. Serotonin receptors in the human brain. II Characterization and autoradiographic localization of 5-HT1C and 5-HT2 recognition sites. Brain Res. 376:97–107.

    Google Scholar 

  22. Pazos, A., Cortés, R., and Palacios, J. M. 1985. Quantitative autoradiographic mapping of serotonin receptors in the rat brain. II. Serotonin-2 receptors. Brain Res. 346:231–249.

    Google Scholar 

  23. Leysen, J. E., Niemegeers, C. J. E., Van Neuten, J. M., and Laduron, P. M. 1982. [3H]-ketanserin (R41468), a selective ligand for 5HT2 receptor binding sites. Mol. Pharmacol. 21:301–314.

    Google Scholar 

  24. Lowry, O. H., Resbrough, N. J., Faer, A. L., and Randall, R. J. 1951. Protein measurement with Folin phenol reagent. J. Biol. Chem., 193:265–275.

    Google Scholar 

  25. Peterson, G. L. 1977. A simplification of the protein assay method which is more generally applicable. Anal. Biochem. 83:356–366.

    Google Scholar 

  26. Mc Pherson, G. A. 1985. KINETIC, EBDA, LIGAND, LOWRY: a collection of radio ligand binding analysis programs. Biosoft, Cambridge, UK.

    Google Scholar 

  27. Nabeshima, T., Yamada, K., Hayashi, T., Hasegawa, T., Ishihara, S., Kameyana, T., Morimasa, T., Kaneyuki, T., and Shohmori, T. 1994. Changes in muscarinic cholinergic, PCP, GABAA, D1 and 5HT2A receptor binding, but not in benzodiazepine receptor binding in the brains of aged rats. Life Sci. 55:1585–1593.

    Google Scholar 

  28. Cross, A. J., Crow, T. J., Gerrier, I. N., Johnson, J. A., Bloom, S. R., and Corsellis, J. A. N. 1984. Serotonin receptor changes in dementia of the Alzheimer's type. J. Neurochem. 43:1574–1581.

    Google Scholar 

  29. Schotte, A., Maloteaux, J. M., and Laduron, P. M. 1983. Characterization and regional distribution of serotonin S2-receptors in human brain. Brain Res. 276:231–235.

    Google Scholar 

  30. Stam, N. J., Van Huizen, F., Van Alebeek, C., Brands, J., Dijkema, R., Tonnaer, J. A. D. M., and Olijve, W. 1992. Genomic organization, coding sequence and functional expression of human 5HT2 and 5HT1A receptor genes. Eur. J. Pharmacol. 227:153–162.

    Google Scholar 

  31. Kane, J., Honigfield, G., Singer, J., Meltzer, H. Y., and the clozaril collaborative study group. 1988. Clozapine for the treatment-resistant schizophrenia. Arch. Gen. Psychiatry 45:789–796.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Istituto di Psichiatria, Università di Pisa, via Roma 67, I-56100, Pisa, Italia

    Donatella Marazziti, Lionella Palego & Giovanni B. Cassano

  2. Istituto Policattedra di Discipline Biologiche, Università di Pisa, via Roma 67, I-56100, Pisa, Italia

    Alessandra Rossi, Gino Giannaccini & Antonio Lucacchini

  3. Istituto di Anatomia Patologica, Università di Pisa, via Roma 67, I-56100, Pisa, Italia

    Antonio Naccarato

Authors
  1. Donatella Marazziti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Alessandra Rossi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lionella Palego
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gino Giannaccini
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Antonio Naccarato
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Antonio Lucacchini
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Giovanni B. Cassano
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Donatella Marazziti.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Marazziti, D., Rossi, A., Palego, L. et al. [3H]Ketanserin Binding in Human Brain Postmortem. Neurochem Res 22, 753–757 (1997). https://doi.org/10.1023/A:1027366413289

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/A:1027366413289

Search

Navigation