Skip to main content
SpringerLink
Log in

Brain 5-HT1 and 5-HT2 binding sites following portacaval shunt in the rat

  • Original Papers
  • Published:
Research in Experimental Medicine

Summary

Brain serotonin 5-HT1 and 5-HT2 binding properties were investigated in experimental chronic portal-systemic encephalopathy (PSE). Endto-side portacaval shunted (PCS) rats were subjected to open field behavioral testing (spontaneous activity and exploration) 3 weeks after the shunt procedure. Each individual animal was then assayed for 5-HT1 and 5-HT2 binding properties (Bmax and KD) in the cortex + hippocampus by the use of radioligand binding and rapid filtration technique. (3H)serotonin was used to label 5-HT1 binding sites and (3H)ketanserin to label 5-HT2 binding sites. Results revealed that the PCS rats exhibited significant behavioral changes with decreased spontaneous activity and exploratory behavior as compared with sham-operated controls (sham). The affinity for, and the number of, 5-HT1 and 5-HT2 binding sites, respectively, were not different between PCS and sham rats. The brain 5-HT1 and 5-HT2 binding porperties were within the range of Bmax and KD previously reported for normal rats when similar techniques are used. This first report in PCS rats on the subject of brain 5-HT1 and 5-HT2 binding properties demonstrates that no major alterations are likely to occur. This contrasts the knowledge of a markedly increased brain serotonin synthesis rate in the PCS rat, suggesting minor functional relevance of the perturbed brain serotonin metabolism associated with chronic PSE.

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. Bengtsson F, Gage FH, Jeppsson B, Nobin A, Rosengren E (1985) Brain monamine metabolism and behavior in portacaval-shunted rats. Exp Neurol 90:21–35

    PubMed  Google Scholar 

  2. Bengtsson F, Nobin A, Falck B, Gage FH, Jeppsson B (1986) Portacaval shunt in the rat: Selective alterations in behavior and brain serotonin. Pharmacol Biochem Behav 24:1611–1616

    PubMed  Google Scholar 

  3. Bengtsson F, Bugge M, Brun A, Falck B, Henriksson K-G, Nobin A (1988) The impact of time after portacaval shunt in the rat on behavior, brain serotonin, and brain and muscle histology. J Neurol Sci 83:109–122

    PubMed  Google Scholar 

  4. Blurton PA, Wood MD (1986) Identification of multiple binding sites for (3H)5-hydroxytryptamine in the rat CNS. J Neurochem 46:1392–1398

    PubMed  Google Scholar 

  5. Bradley PB, Engel G, Feniuk W, Fozard JR, Humphrey PPA, Middlemiss DN, Mylecharane EJ, Richardson BP, Saxena PR (1986) Proposals for the classification and nomenclature of functional receptors for 5-hydroxytryptamine. Neuropharmacology 25:563–576

    PubMed  Google Scholar 

  6. Conn HO, Lieberthal MM (1979) The hepatic coma syndromes and lactulose. Williams & Wilkins, Baltimore, pp 46–121

    Google Scholar 

  7. Doumas BT (1975) Standards for total serum protein assays — a collaborative study. Clin Chem 21:1159–1166

    PubMed  Google Scholar 

  8. Fischer JE, Baldessarini RJ (1976) Pathogenesis and therapy of hepatic coma. Prog Liver Dis 5:363–397

    PubMed  Google Scholar 

  9. Glowinski J (1975) Properties and functions of intraneuronal monoamine compartments in central aminergic neurons. In: Iversen LL, Iversen SD, Snyder SH (eds) Handbook of psychopharmacology. Plenum Press, New York, pp 136–167

    Google Scholar 

  10. Grahame-Smith DG (1973) Does the total turnover of brain 5-HT reflect the functional activity of 5-HT in brain? In: Barchas J, Usdin E (eds) Serotonin and behavior. Academic Press, New York, pp 5–7

    Google Scholar 

  11. Hall H, Wedel I (1985) The effect of manipulations of presynaptic 5-HT nerve terminals on postsynaptic 5-HT1 and 5-HT2 binding sites of the rat brain. J Neural Transm 64:129–143

    PubMed  Google Scholar 

  12. Herrick-Davis K, Titeler M (1988) Detection and characterization of the serotonin 5-HT1D receptor in rat and human brain. J Neurochem 50:1624–1631

    PubMed  Google Scholar 

  13. Holmin T, Siesjö BK (1974) The effect of porta-caval anastomosis upon the energy state and upon acid-base parameters of the rat brain. J Neurochem 22:403–412

    PubMed  Google Scholar 

  14. Kienzl E, Riederer P, Jellinger K, Roth E, Ferenci P (1984) Modulation of serotonin receptors by L-valine in hepatic encephalopathy. In: Schlossberger et al. (eds) Progress in tryptophan and serotonin research. Walter de Gruyter, Berlin, pp 333–337

    Google Scholar 

  15. Kilpatrick GJ, Jones BJ, Tyers MB (1988) Identification and distribution of 5-HT3 receptors in rat brain using radioligand binding. Nature 330:746–748

    Google Scholar 

  16. Leysen JE (1985) Characterization of serotonin receptor binding sites. In: Green AR (ed) Neuropharmacology of serotonin. Oxford University Press, pp 79–116

  17. Leysen JE, Niemegeers CJE, Van Nueten JM, Laduron PM (1982) (3H)Ketanserin (R 41468) a selective (3H)ligand for serotonin2 receptor binding sites. Mol Pharmacol 21:301–314

    PubMed  Google Scholar 

  18. Lowry OH, Rosebrough MJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193:265–275

    PubMed  Google Scholar 

  19. Martin JR, Baettig K, Bircher J (1980) Maze patrolling, open-field behavior and runway activity following experimental portacaval anastomosis in rats. Physiol Behav 25:713–719

    PubMed  Google Scholar 

  20. Munson PJ, Rodbard D (1980) Ligand: A versatile computerized approach for the characterization of ligand binding systems. Anal Biochem 107:220–239

    PubMed  Google Scholar 

  21. Peroutka SJ, Snyder SH (1979) Multiple serotonin receptors: Differential binding of (3H)5-hydroxytryptamine, (3H)lysergic acid diethylamide and (3H)spiroperidol. Mol Pharmacol 16:687–699

    PubMed  Google Scholar 

  22. Riederer P, Kruzik P, Kienzl E, Kleinberger G, Jellinger K, Wesemann W (1984) Molecular aspects of neurotransmitter-receptor changes in hepatic encephalopathy. In: Kleinberger G, Ferenci P, Riederer P, Thaler H (eds) Advances in hepatic encephalopathy and urea cycle diseases. Karger, Basel, pp 373–384

    Google Scholar 

  23. Savage DD, Mendels J, Frazer A (1980) Monoamine oxidase inhibitors and serotonin uptake inhibitors: Differentiated effects on (3H)serotonin binding sites in rat brain. J Pharmacol Exp Ther 212:259–263

    PubMed  Google Scholar 

  24. Scatchard G (1949) The attractions of proteins for small molecules and ions. Ann NY Acad Sci 51:660–672

    Google Scholar 

  25. Schröder R, Müller O, Bircher J (1985) The portacaval and splenocaval shunt in the normal rat. A morphological and functional reevaluation. J Hepatol 1:107–123

    PubMed  Google Scholar 

  26. Shields PJ, Eccleston D (1973) Evidence for the synthesis and storage of 5-hydroxytryptamine in two separate pools in the brain. J Neurochem 20:881–888

    PubMed  Google Scholar 

  27. Warbritton JD, Geyer MA, Jeppsson B, Fischer JE (1980) Decreased startle reactivity in the end-to-side portacaval shunted rat. Pharmacol Biochem Behav 12:739–742

    PubMed  Google Scholar 

  28. Wesemann W, Weiner N, Rotsch M, Schulz E (1983) Serotonin binding in rat brain: Circadian rhythm and effect of sleep deprivation. J Neural Transm 18:287–294

    Google Scholar 

  29. Yamamura HI, Enna SJ, Kuhar MJ (1978) Neurotransmitter receptor binding. Raven Press, New York

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Dept. of Surgery, Lund University, Lund, Sweden

    F. Bengtsson, M. Bugge & A. Nobin

  2. Dept. of Biochemical Neuropharmacology, Research and Development Laboratories, Astra Alab AB, Södertälje, Sweden

    H. Hall

Authors
  1. F. Bengtsson
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. M. Bugge
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. H. Hall
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A. Nobin
    View author publications

    You can also search for this author in PubMed Google Scholar

Additional information

Financially supported by the Medical Faculty, Lund University, Sweden, the “Förenade Liv” Mutual Group Life Insurance Company, Stockholm, Sweden, the Swedish Society of Medicine, and the Swedish Medical Research Council (grants 12X-712 and 14X-56)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bengtsson, F., Bugge, M., Hall, H. et al. Brain 5-HT1 and 5-HT2 binding sites following portacaval shunt in the rat. Res. Exp. Med. 189, 249–256 (1989). https://doi.org/10.1007/BF01852256

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01852256

Key words

Search

Navigation