Skip to main content
SpringerLink
Log in
Book cover

Cardiovascular Pharmacology of 5-Hydroxytryptamine pp 127–142Cite as

Allosteric modulation of arterial 5-HT2 receptors

  • Chapter

Abstract

Interaction of arterial 5-HT2 receptors with their ligands are variable and complex. Some produce a surmountable, apparently competitive inhibition of the effects of 5-hydroxytryptamine (5-HT), causing a simple rightward shift of the concentration-effect curve for 5-HT. Other antagonists cause a rightward shift of the concentration-effect curve and a depression of maximum responses to 5-HT which cannot be surmounted by increased concentrations of 5-HT. However, in some cases, the unsurmountable action of one antagonist can be prevented or reversed by exposure to another, surmountable antagonist.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   39.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   54.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Kaumann AJ, Frenken M (1985): A paradox: the 5-HT2 receptor antagonist ketanserin restores the 5-HT-induced contraction depressed by methysergide in large coronary arteries of calf. Allosteric regulation of 5-HT2 receptors. Naunyn-Schmiedeberg’s Arch Pharmacol 328: 295–300.

    Article  CAS  Google Scholar 

  2. Peroutka SJ, Snyder SH (1979): Multiple serotonin receptors: Differential binding of [3H]-5-hydroxy tryptamine [3H]lysergic acid diethylamide and [3H]-spiroperidol. Mol Pharmacol16: 687–699.

    CAS  PubMed  Google Scholar 

  3. Clancy M, Maayani S (1985): 5-Hydroxytryptamine receptor in isolated rabbit aorta. Characterisation with tryptamine analogs. J Pharmacol Exp Ther233:761–769.

    CAS  PubMed  Google Scholar 

  4. Frenken M, Kaumann AJ (1987): Interconversion into a low active state protects vascular 5-HT2 receptors against irreversible antagonism by phenoxybenzamine. Naunyn-Schmiedeberg’s Arch Pharmacol335: 481–490.

    CAS  Google Scholar 

  5. Van Nueten JM, Janssen PAJ, van Beck J, Xhonneux R, Verbeuren TJ, Vanhoutte PM (1981): Vascular effects of ketanserin (R 41468), a novel antagonist of 5-HT2 serotonergic receptors. J Pharmacol Exp Ther218: 217–230.

    PubMed  Google Scholar 

  6. Kaumann AJ (1983): Yohimbine and rauwolscine inhibit 5-HT2 receptors. Naunyn-Schmiedeberg’s Arch Pharmacol333: 149–154.

    Article  Google Scholar 

  7. Freedman SB, Chierchia S, Rodriguez-Plaza L, Burgiardini R, Smith G, Maseri A (1984): Ergonovine-induced myocardial ischaemia: no role for serotonergic receptors? Circulation70, 178–183.

    CAS  Google Scholar 

  8. Frenken M, Kaumann AJ (1985): Ketanserin causes surmountable antagonism of 5-hydroxytryptamine-induced contractions in large coronary arteries of dog. Naunyn-Schmiedeberg’s Arch Pharmacol328: 301–303.

    Article  CAS  Google Scholar 

  9. Frenken M, Kaumann AJ (1986): Surmountable antagonism by ketanserin of 5-hydroxy-tryptamine-induced contractions in dog basilar artery. Br J Pharmac89: 550 P.

    Google Scholar 

  10. Gaddum JH, Hameed KA (1954): Drugs which antagonize 5-hydroxytryptamine. Br J Pharmac9: 240–248.

    CAS  Google Scholar 

  11. Kaumann AJ (1989): The allosteric 5-HT2 receptor system, in: Fozard J (ed) The peripheral actions of 5-hydroxytryptamine. Oxford University Press pp. 45–71.

    Google Scholar 

  12. Kaumann AJ, Frenken M (1988): ICI 169,369 is both a competitive antagonist and an allosteric activator of the arterial 5-hydroxytryptamine2 receptor system. J Pharmacol Exp Ther245: 1010–1015.

    CAS  PubMed  Google Scholar 

  13. Lemoine H, Kaumann AJ (1986): Allosteric properties of 5-HT2 receptors in tracheal smooth muscle. Naunyn-Schmiedeberg’s Arch Pharmacol333: 91–97.

    Article  CAS  Google Scholar 

  14. Sampford KA, Kaumann AJ (1988): ICI 169,369 is both a competitive antagonist and activator of the 5-HT2 receptor system of guinea-pig trachea. Br J Pharmacol95: 775 P.

    Google Scholar 

  15. Frenken M, Kaumann AJ (1987): Allosteric properties of the 5-HT2 receptor system of the rat tail artery —Ritanserin and methysergide are not competitive 5-HT2 receptor antagonists but allosteric modulators. Naunyn-Schmiedeberg’s Arch Pharmacol335: 359–366.

    Article  CAS  Google Scholar 

  16. Blackburn TP, Thornber CW, Pearce RJ, Cox B (1988): In vitro pharmacology of ICI 170,809— a new 5-HT2 antagonist. Abstract. FASEB Journal5(2): A 1404.

    Google Scholar 

  17. Frenken M, Kaumann AJ (1989): Dimethylation of the activator ICI 169,369 results in a high-affinity partial deactivator, ICI 170,809, of the arterial 5-HT2 receptor system. J Pharmacol Exp Ther250: 707–713.

    CAS  PubMed  Google Scholar 

  18. Kaumann AJ (1987): A two-state model for the 5-HT2 receptor. Biol Chem Hoppe-Seyler368: 1131–1132.

    Article  Google Scholar 

  19. Cohen ML, Fuller RW, Kurz KD (1983): LY 53857, a selective and potent serotonergic (5-HT2) receptor antagonist does not lower blood pressure in spontaneously hypertensive rat. J Pharmacol Exp Ther227: 327–332.

    CAS  PubMed  Google Scholar 

  20. Barrett VJ, Leff P, Martin GR, Richardson PJ (1986): Pharmacological analysis of the interaction between Bay K8644 and 5-HT in rabbit aorta. Br J Pharmac87: 487–494.

    Article  CAS  Google Scholar 

  21. Frenken M, Kaumann AJ (198): Effects of tryptamine mediated through 2 states of the 5-HT2 receptor in calf coronary artery. Naunyn-Schmiedeberg’s Arch Pharmacol337: 484–492.

    Article  CAS  Google Scholar 

  22. Kaumann AJ (1988): A two-state model for the 5-HT2 receptor: Effects of a-adrenoceptor ligands. J Cardiovasc Pharmacol11 (suppl 1): S88– S92.

    Article  PubMed  Google Scholar 

  23. Doyle VM, Creba JA, Ruegg UT, Hoyer D (1986): Serotonin increases production of inositol phosphates and mobilises calcium via the 5-HT2 receptor in A7r5 smooth muscle cells. Naunyn-Schmiedeberg’s Arch Pharmacol333: 98–103.

    Article  CAS  Google Scholar 

  24. Lemoine H, Pohl V, Teng KJ (1988): Serotonin (5-HT) stimulates phosphatidyl inositol (Pi) hydrolysis only through the R-state of allosterically regulated 5-HT2 receptors in calf tracheal smooth muscle. Naunyn-Schmiedeberg’s Arch Pharmacol337: R103.

    Google Scholar 

  25. Nakaki T, Roth BL, Chuang DM, Costa E (1985): Phasic and tonic components in 5-HT2 receptor-mediated rat aorta contraction. Participation of Ca++ channels and phospholipase C. J Pharmacol Exp Ther234: 442–446.

    CAS  PubMed  Google Scholar 

  26. Lemoine H, Teng KJ (1989): A mathematical model describing the allosteric regulation of peripheral 5-HT2-receptors. Naunyn-Schmiedeberg’s Arch Pharmacol339: R97.

    Google Scholar 

  27. Kaumann AJ, Brown AM (1989): Differences between allosterism and incomplete equilibrium in the 5-HT2 system. Naunyn-Schmiedeberg’s Arch Pharmacol339: R97.

    Google Scholar 

  28. Frenken M, Kaumann AJ (1984): Interaction of ketanserin and its metabolite ketan-serinol with 5-HT2-receptors in pulmonary and coronary arteries of calf. Naunyn-Schmiedeberg’s Arch Pharmacol326: 334–339.

    Article  CAS  Google Scholar 

  29. Connor HE, FeniukW, Humphrey PPA (1989): 5-Hydroxytryptamine contracts human coronary arteries predominantly via 5-HT2 receptor activation. Eur J Pharmacol161: 91–94.

    Article  CAS  PubMed  Google Scholar 

Download references

Authors
  1. A. J. Kaumann
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. A. M. Brown
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Pharmacology, Erasmus University, Rotterdam, The Netherlands

    P. R. Saxena

  2. Department of Physiology, University of Wales, College of Cardiff, Cardiff, UK

    D. I. Wallis

  3. Department of Pharmacology, Duphar B.V, Weesp, The Netherlands

    W. Wouters  & P. Bevan  & 

Rights and permissions

Reprints and permissions

Copyright information

© 1990 Springer Science+Business Media Dordrecht

About this chapter

Cite this chapter

Kaumann, A.J., Brown, A.M. (1990). Allosteric modulation of arterial 5-HT2 receptors. In: Saxena, P.R., Wallis, D.I., Wouters, W., Bevan, P. (eds) Cardiovascular Pharmacology of 5-Hydroxytryptamine. Developments in CardioCardiovascular Pharmacology of 5-Hydroxytryptamine, vol 106. Springer, Dordrecht. https://doi.org/10.1007/978-94-009-0479-8_10

Download citation

  • DOI: https://doi.org/10.1007/978-94-009-0479-8_10

  • Publisher Name: Springer, Dordrecht

  • Print ISBN: 978-94-010-6701-0

  • Online ISBN: 978-94-009-0479-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation