Topographical distribution of 5-HT3 receptor recognition sites in the ferret brain stem

  • J. M. Barnes
  • N. M. Barnes
  • B. Costall
  • I. L. Naylor
  • R. J. Naylor
  • J. A. Rudd
Article
Received:
Accepted:

Summary

The distribution of [3H]zacopride (1.0 nM) to putative 5-HT3 receptor recognition sites in the ferret hindbrain was assessed using autoradiography. Specific binding (defined by the inclusion of granisetron, 1.0 μM) was heterogeneously distributed with highest density within the dorsal vagal complex (area postrema, nucleus tractus solitarius and dorsal motor nucleus of the vagus nerve). Lower densities were detected in the spinal trigeminal nerve complex whilst no other significant specific binding was detected ventral to the dorsal vagal complex. The location of 5-HT3 receptor recognition sites within the dorsal vagal complex may provide sites of action for zacopride and other 5-HT3 receptor antagonists to inhibit the emesis induced by cancer chemotherapeutic agents and x-radiation.

Key words

5-Hydroxytryptamine3 receptor recognition sites Ferret Brainstem Emesis 
This is a preview of subscription content, log in to check access.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Andrews PLR, Hawthorn J (1987) Evidence for an extra-abdominal site of action for the 5-HT3 receptor antagonist BRL 24924 in the inhibition of radiation-evoked emesis in the ferret. Neuropharmacology 26:1367–1370Google Scholar
  2. Andrews PLR, Bingham S, Davis CJ (1984) Retching evoked by stimulation of abdominal vagal afferents in the anaesthetized ferret. J Physiol (Lond) 358:103PGoogle Scholar
  3. Andrews PLR, Rapeport WG, Sanger GJ (1988) Neuropharmacology of emesis induced by anti-cancer therapy. TIPS 9:334–341Google Scholar
  4. Barnes JM, Barnes NM, Costall B, Naylor RJ, Tattersall FD (1988a) Reserpine, para-chlorophenylalanine and fenfluramine antagonise cisplatin-induced emesis in the ferret. Neuropharmacology 27:783–790Google Scholar
  5. Barnes NM, Costall B, Ironside JW, Naylor RJ (1988b) Identification of 5-HT3 recognition sites in human brain using [3H]zacopride. J Pharm Pharmacol 40:668Google Scholar
  6. Barnes NM, Costall B, Naylor RJ (1988c) [3H]zacopride: ligand for the identification of 5-HT3 recognition sites. J Pharm Pharmacol 40:548–551Google Scholar
  7. Barnes NM, Costall B, Naylor RJ, Tattersall FD (1988d) Identification of 5-HT3 recognition sites in the ferret area postrema. J Pharm Pharmacol 40:586–588Google Scholar
  8. Barnes JM, Barnes NM, Costall B, Ironside JW, Naylor RJ (1989) Identification and characterisation of 5-HT3 recognition sites in human brain tissue. J Neurochem 53:1787–1793Google Scholar
  9. Barnes JM, Barnes NM, Costall B, Deakin JFW, Ironside JW, Kilpatrick GJ, Naylor RJ, Rudd JA, Simpson MJ, Slater P, Tyers MB (1990) Identification and distribution of 5-HT3 recognition sites within the human brain stem. Neurosci Lett 111: 80–86Google Scholar
  10. Bogdanski DF, Weissbach H, Udenfriend S (1958) Pharmacological studies with the serotonin precursor, 5-hydroxytryptophan. J Pharmacol Exp Ther 122:182–194Google Scholar
  11. Borison HL (1973) Area postrema: chemoreceptor trigger zone for vomiting - is that all? Life Sci 14:1807–1817Google Scholar
  12. Borison HL (1984) History and status of the area postrema. Fed Proc 43:2937–2940Google Scholar
  13. Borison HL, Wang SC (1953) Physiology and pharmacology of vomiting. Pharmacol Rev 5:193–230Google Scholar
  14. Borison HL, Borison BA, McCarthy LE (1981) Phylogenic and neurologic aspects of the vomiting process. J Clin Pharmacol 21:23S-29SGoogle Scholar
  15. Brizzee KR (1956) Effect of localized brain stem lesions and supradiaphragmatic vagotomy on X-irradiation emesis in the monkey. Am J Physiol 187:567–570Google Scholar
  16. Carmichael J, Cantwell BMJ, Edwards CM, Rapeport WG, Harris AL (1988) The serotonin type 3 receptor antagonist BRL 43694 and nausea and vomiting induced by cisplatin. Br Med J 297:110–111Google Scholar
  17. Carpenter DO, Briggs DB, Strominger N (1983) Responses of neurons of canine area postrema to neurotransmitters and peptides. Cell Mol Neurobiol 3:113–126Google Scholar
  18. Carpenter DO, Briggs DB, Knox AP, Strominger NL (1986) Radiation-induced emesis in the dog: effects of lesions and drugs. Radiat Res 108:307–316Google Scholar
  19. Chadwick D, Reynolds EH, Marsden CD (1974) Relief of action myoclonus by 5-hydroxytryptophan. Lancet 11:111–112Google Scholar
  20. Costall B, Domeney AM, Naylor RJ, Tattersall FD (1987) Emesis induced by cisplatin in the ferret as a model for the detection of anti-emetic drugs. Neuropharmacology 26:1321–1326Google Scholar
  21. Cunningham D, Hawthorn J, Pople A, Gazet J-C, Ford HT, Challoner T, Coombes RC (1987) Prevention of emesis in patients receiving cytotoxic drugs by GR38032F, a selective 5-HT3 receptor antagonist. Lancet I:1461–1463Google Scholar
  22. Engelman K, Lovenberg W, Sjoerdsma A (1967) Inhibition of serotonin synthesis by para-chlorophenylalanine in patients with carcinoid syndrome. N Eng] J Med 277:1103–1108Google Scholar
  23. Hamon H, Gallissot MC, Menard F, Gozlan H, Bourgoin S, Verge D (1989) 5-HT3 receptor binding sites are on capsaicin-sensitive fibres in the rat spinal cord. Eur J Pharmacol 164:315–322Google Scholar
  24. Hawthorn J, Ostler KJ, Andrews PLR (1988) The role of the abdominal visceral innervation and 5-hydroxytryptamine M-receptors in vomiting induced by the cytotoxic drugs cyclophosphamide and cisplatin in the ferret. Q J Exp Physiol 73:7–21Google Scholar
  25. Higgins GA, Kilpatrick GJ, Bunce KT, Jones BJ, Tyers MB (1989) 5-HT3 receptor antagonists injected into the area postrema inhibit cisplatin-induced emesis in the ferret. Br J Pharmacol 97:247–255Google Scholar
  26. Hoyer D, Waeber C, Karpf A, Neijt H, Palacios JM (1989) [3H]ICS 205–930 labels 5-HT3 recognition sites in membranes of cat and rabbit vagus nerve and superior cervical ganglion. Naunyn-Schmiedeberg's Arch Pharmacol 340:396–402Google Scholar
  27. Hyde TM, Miselis RR (1983) Effects of area postrema/caudal medial nucleus of solitary tract lesions on food intake and body weight. Am J Physiol 244:R577-R587Google Scholar
  28. Ireland SJ, Tyers MB (1987) Pharmacological characterisation of 5-hydroxytryptamine-induced depolarisation of the rat isolated vagus nerve. Br J Pharmacol 90:229–238Google Scholar
  29. Kilpatrick GJ, Jones BJ, Tyers MB (1989) Binding of the 5-HT3 ligand, [3H]GR65630, to rat area postrema, vagus nerve and the brains of several species. Eur J Pharmacol 159:157–164Google Scholar
  30. Leibundgut U, Lancranjan I (1987) First results with ICS 205–930 (5-HT3 receptor antagonist) in prevention of chemotherapy induced emesis. Lancet I:1198Google Scholar
  31. Leslie RA (1985) Neuroactive substances in the dorsal vagal complex of the medulla oblongata: nucleus of the tractus solitarius, area postrema and dorsal motor nucleus of the vagus. Neurochem Int 7(2):191–211Google Scholar
  32. Leslie RA (1986) Comparative aspects of the area postrema: finestructural considerations help to determine its function. Cell Mol Neurobiol 6:95–120Google Scholar
  33. Leslie RA, Gwyn DG (1984) Neuronal connections of the area postrema. Fed Proc 43: 2941–2943Google Scholar
  34. Lindstrom PA, Brizzee KR (1962) Relief of intractable vomiting from surgical lesions in the area postrema. J Neurosurg 19: 228–236Google Scholar
  35. Lucot JB (1989) Blockade of 5-hydroxytryptamine3 receptors prevents cisplatin-induced but not motion- or xylazine-induced emesis in the cat. Pharmacol Biochem Behav 32:207–210Google Scholar
  36. Magnussen I, Nielsen-Kudsk F (1979) Pharmacokinetics of intravenously administered L-5-hydroxytryptophan in man. Acta Pharmacol Toxicol 44:308–314Google Scholar
  37. Marty M, Droz JP, Pouillart P, Paule B, Brion N, Bons J (1989) GR38032F, a 5-HT3 receptor antagonist, in the prophylaxis of acute cisplatin-induced nausea and vomiting. Cancer Chemother Pharmacol 23:389–391Google Scholar
  38. McCarthy LE, Borison HL (1984) Cisplatin-induced vomiting eliminated by ablation of the area postrema in cats. Cancer Treat Rep 68:401–404Google Scholar
  39. Miner WD, Sanger GJ (1986) Inhibition of cisplatin-induced vomiting by selective 5-hydroxytryptamine M-receptor antagonism. Br J Pharmacol 88:497–499Google Scholar
  40. Pinkus LM, Sarbin NS, Barefoot DS, Gordon JC (1989) Association of [3H]zacopride with 5-HT3 binding sites. Eur J Pharmacol 168:355–362Google Scholar
  41. Pratt GD, Bowery NG (1989) The 5-HT3 receptor ligand, [3H]BRL43694, binds to presynaptic sites in the nucleus tractus solitarius of the rat. Br J Pharmacol 97 [Suppl]:414PGoogle Scholar
  42. Reynolds DJM, Andrews PLR, Leslie RA, Harvey JM, Grasby PM, Grahame-Smith DG (1989) Bilateral vagotomy abolishes binding of [3H]BRL43694 in ferret dorsovagal complex. Br J Pharmacol 98 [Suppl]:692PGoogle Scholar
  43. Richardson BP, Buchheit K-H (1988) The pharmacology, distribution and function of 5-HT3 receptors. In: Osborne NN, Hamon M (eds) Neuronal serotonin. Wiley, Chichester, pp 465–506Google Scholar
  44. Sanger GJ, Nelson DR (1989) Selective and functional 5-hydroxytryptamine3 receptor antagonism by BRL43694 (granisetron). Eur J Pharmacol 159:113–124Google Scholar
  45. Smith WL, Callahan EM, Alphin RS (1988) Emetic activity of centrally administered cisplatin in cats and its antagonism by zacopride. J Pharm Pharmacol 40:142–143Google Scholar
  46. Smith WL, Alphin RS, Jackson CB, Sancilio LF (1989) The antiemetic profile of zacopride. J Pharm Pharmacol 41:101–105Google Scholar
  47. Smith WW, Sancilio LF, Owera-Atepo JB, Naylor RJ, Lambert LL (1988) Zacopride, a potent 5-HT3 antagonist. J Pharm Pharmacol 40:301–302Google Scholar
  48. Waeber C, Dixon K, Hoyer D, Palacios JM (1988) Localisation by autoradiography of neuronal 5-HT3 receptors in the mouse CNS. Eur J Pharmacol 151:351–352Google Scholar
  49. Waeber C, Hoyer D, Palacios JM (1989) 5-Hydroxytryptamine3 receptors in the human brain: autoradiographic visualization using [3H]ICS 205–930. Neuroscience 31:393–400Google Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • J. M. Barnes
    • 1
  • N. M. Barnes
    • 1
  • B. Costall
    • 1
  • I. L. Naylor
    • 1
  • R. J. Naylor
    • 1
  • J. A. Rudd
    • 1
  1. 1.Postgraduate Studies in Pharmacology, The School of PharmacyUniversity of BradfordBradfordUK

Personalised recommendations