Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1994 Apr 26;91(9):3666–3669. doi: 10.1073/pnas.91.9.3666

Selective 5-HT1D alpha serotonin receptor gene expression in trigeminal ganglia: implications for antimigraine drug development.

G W Rebeck 1, K I Maynard 1, B T Hyman 1, M A Moskowitz 1
PMCID: PMC43642  PMID: 8170966

Abstract

Pharmacological data suggest that the actions of antimigraine drugs such as sumatriptan may be mediated by 5-HT1D-like serotonin receptors on trigeminovascular nerve endings. We sought molecular evidence for the expression of an mRNA species encoding the 5-HT1D receptor subtype in guinea pig and human trigeminal ganglia, using the polymerase chain reaction with oligonucleotides uniquely homologous to the coding sequences of the 5-HT1B/D family (human 5-HT1D alpha and 5-HT1D beta; rat 5-HT1B). A single band of predicted size was observed in samples from guinea pig trigeminal ganglia; sequence analysis revealed the presence of a single message, which was 85% and 71% identical to the human 5-HT1D alpha and 5-HT1D beta receptor DNA sequences, respectively. Similar analyses of postmortem human trigeminal ganglia revealed the presence of 5-HT1D alpha, but not 5-HT1D beta, receptor message. Inasmuch as one recent report found that mRNA encoding only the 5-HT1D beta receptor subtype was expressed by vascular smooth muscle of the central nervous system, the present findings suggest the importance of developing selective 5-HT1D alpha receptor agonists as a strategy to reduce the risk of myocardial infarction and possibly stroke that complicates the acute treatment of migraine headache.

Full text

PDF
3666

Images in this article

3667Image
on p.3667
3668Image
on p.3668
3668Image
on p.3668

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Adham N., Kao H. T., Schecter L. E., Bard J., Olsen M., Urquhart D., Durkin M., Hartig P. R., Weinshank R. L., Branchek T. A. Cloning of another human serotonin receptor (5-HT1F): a fifth 5-HT1 receptor subtype coupled to the inhibition of adenylate cyclase. Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):408–412. doi: 10.1073/pnas.90.2.408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Amlaiky N., Ramboz S., Boschert U., Plassat J. L., Hen R. Isolation of a mouse "5HT1E-like" serotonin receptor expressed predominantly in hippocampus. J Biol Chem. 1992 Oct 5;267(28):19761–19764. [PubMed] [Google Scholar]
  3. Bach A. W., Unger L., Sprengel R., Mengod G., Palacios J., Seeburg P. H., Voigt M. M. Structure functional expression and spatial distribution of a cloned cDNA encoding a rat 5-HT1D-like receptor. J Recept Res. 1993;13(1-4):479–502. doi: 10.3109/10799899309073674. [DOI] [PubMed] [Google Scholar]
  4. Bateman D. N. Sumatriptan. Lancet. 1993 Jan 23;341(8839):221–224. doi: 10.1016/0140-6736(93)90079-v. [DOI] [PubMed] [Google Scholar]
  5. Bruinvels A. T., Landwehrmeyer B., Moskowitz M. A., Hoyer D. Evidence for the presence of 5-HT1B receptor messenger RNA in neurons of the rat trigeminal ganglia. Eur J Pharmacol. 1992 Nov 2;227(3):357–359. doi: 10.1016/0922-4106(92)90017-p. [DOI] [PubMed] [Google Scholar]
  6. Buzzi M. G., Dimitriadou V., Theoharides T. C., Moskowitz M. A. 5-Hydroxytryptamine receptor agonists for the abortive treatment of vascular headaches block mast cell, endothelial and platelet activation within the rat dura mater after trigeminal stimulation. Brain Res. 1992 Jun 26;583(1-2):137–149. doi: 10.1016/s0006-8993(10)80017-4. [DOI] [PubMed] [Google Scholar]
  7. Buzzi M. G., Moskowitz M. A., Peroutka S. J., Byun B. Further characterization of the putative 5-HT receptor which mediates blockade of neurogenic plasma extravasation in rat dura mater. Br J Pharmacol. 1991 Jun;103(2):1421–1428. doi: 10.1111/j.1476-5381.1991.tb09805.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Buzzi M. G., Moskowitz M. A. The antimigraine drug, sumatriptan (GR43175), selectively blocks neurogenic plasma extravasation from blood vessels in dura mater. Br J Pharmacol. 1990 Jan;99(1):202–206. doi: 10.1111/j.1476-5381.1990.tb14679.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  10. Ferrari M. D., Saxena P. R. Clinical and experimental effects of sumatriptan in humans. Trends Pharmacol Sci. 1993 Apr;14(4):129–133. doi: 10.1016/0165-6147(93)90084-w. [DOI] [PubMed] [Google Scholar]
  11. Hamblin M. W., Metcalf M. A. Primary structure and functional characterization of a human 5-HT1D-type serotonin receptor. Mol Pharmacol. 1991 Aug;40(2):143–148. [PubMed] [Google Scholar]
  12. Hamel E., Bouchard D. Contractile 5-HT1 receptors in human isolated pial arterioles: correlation with 5-HT1D binding sites. Br J Pharmacol. 1991 Jan;102(1):227–233. doi: 10.1111/j.1476-5381.1991.tb12158.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hamel E., Fan E., Linville D., Ting V., Villemure J. G., Chia L. S. Expression of mRNA for the serotonin 5-hydroxytryptamine1D beta receptor subtype in human and bovine cerebral arteries. Mol Pharmacol. 1993 Aug;44(2):242–246. [PubMed] [Google Scholar]
  14. Hartig P. R., Branchek T. A., Weinshank R. L. A subfamily of 5-HT1D receptor genes. Trends Pharmacol Sci. 1992 Apr;13(4):152–159. doi: 10.1016/0165-6147(92)90053-9. [DOI] [PubMed] [Google Scholar]
  15. Humphrey P. P., Feniuk W. Mode of action of the anti-migraine drug sumatriptan. Trends Pharmacol Sci. 1991 Dec;12(12):444–446. doi: 10.1016/0165-6147(91)90630-b. [DOI] [PubMed] [Google Scholar]
  16. Jin H., Oksenberg D., Ashkenazi A., Peroutka S. J., Duncan A. M., Rozmahel R., Yang Y., Mengod G., Palacios J. M., O'Dowd B. F. Characterization of the human 5-hydroxytryptamine1B receptor. J Biol Chem. 1992 Mar 25;267(9):5735–5738. [PubMed] [Google Scholar]
  17. Lovenberg T. W., Erlander M. G., Baron B. M., Racke M., Slone A. L., Siegel B. W., Craft C. M., Burns J. E., Danielson P. E., Sutcliffe J. G. Molecular cloning and functional expression of 5-HT1E-like rat and human 5-hydroxytryptamine receptor genes. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2184–2188. doi: 10.1073/pnas.90.6.2184. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Matsubara T., Moskowitz M. A., Byun B. CP-93,129, a potent and selective 5-HT1B receptor agonist blocks neurogenic plasma extravasation within rat but not guinea-pig dura mater. Br J Pharmacol. 1991 Sep;104(1):3–4. doi: 10.1111/j.1476-5381.1991.tb12374.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Molderings G. J., Werner K., Likungu J., Göthert M. Inhibition of noradrenaline release from the sympathetic nerves of the human saphenous vein via presynaptic 5-HT receptors similar to the 5-HT 1D subtype. Naunyn Schmiedebergs Arch Pharmacol. 1990 Oct;342(4):371–377. doi: 10.1007/BF00169451. [DOI] [PubMed] [Google Scholar]
  20. Moskowitz M. A. Neurogenic versus vascular mechanisms of sumatriptan and ergot alkaloids in migraine. Trends Pharmacol Sci. 1992 Aug;13(8):307–311. doi: 10.1016/0165-6147(92)90097-p. [DOI] [PubMed] [Google Scholar]
  21. Moskowitz M. A., Nozaki K., Kraig R. P. Neocortical spreading depression provokes the expression of c-fos protein-like immunoreactivity within trigeminal nucleus caudalis via trigeminovascular mechanisms. J Neurosci. 1993 Mar;13(3):1167–1177. doi: 10.1523/JNEUROSCI.13-03-01167.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Murphy T. J., Bylund D. B. Characterization of serotonin-1B receptors negatively coupled to adenylate cyclase in OK cells, a renal epithelial cell line from the opossum. J Pharmacol Exp Ther. 1989 May;249(2):535–543. [PubMed] [Google Scholar]
  23. Nguyen T., Marchese A., Kennedy J. L., Petronis A., Peroutka S. J., Wu P. H., O'Dowd B. F. An Alu sequence interrupts a human 5-hydroxytryptamine1D receptor pseudogene. Gene. 1993 Feb 28;124(2):295–301. doi: 10.1016/0378-1119(93)90409-v. [DOI] [PubMed] [Google Scholar]
  24. Nozaki K., Moskowitz M. A., Boccalini P. CP-93,129, sumatriptan, dihydroergotamine block c-fos expression within rat trigeminal nucleus caudalis caused by chemical stimulation of the meninges. Br J Pharmacol. 1992 Jun;106(2):409–415. doi: 10.1111/j.1476-5381.1992.tb14348.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Ottervanger J. P., Paalman H. J., Boxma G. L., Stricker B. H. Transmural myocardial infarction with sumatriptan. Lancet. 1993 Apr 3;341(8849):861–862. doi: 10.1016/0140-6736(93)93064-8. [DOI] [PubMed] [Google Scholar]
  26. Peroutka S. J., McCarthy B. G. Sumatriptan (GR 43175) interacts selectively with 5-HT1B and 5-HT1D binding sites. Eur J Pharmacol. 1989 Apr 12;163(1):133–136. doi: 10.1016/0014-2999(89)90406-8. [DOI] [PubMed] [Google Scholar]
  27. Ruffolo R. R., Jr, Waddell J. E. Receptor interactions of imidazolines: alpha-adrenoceptors of rat and rabbit aortae differentiated by relative potencies, affinities and efficacies of imidazoline agonists. Br J Pharmacol. 1982 Sep;77(1):169–176. doi: 10.1111/j.1476-5381.1982.tb09283.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Saito K., Markowitz S., Moskowitz M. A. Ergot alkaloids block neurogenic extravasation in dura mater: proposed action in vascular headaches. Ann Neurol. 1988 Dec;24(6):732–737. doi: 10.1002/ana.410240607. [DOI] [PubMed] [Google Scholar]
  29. Schlicker E., Fink K., Göthert M., Hoyer D., Molderings G., Roschke I., Schoeffter P. The pharmacological properties of the presynaptic serotonin autoreceptor in the pig brain cortex conform to the 5-HT1D receptor subtype. Naunyn Schmiedebergs Arch Pharmacol. 1989 Jul;340(1):45–51. doi: 10.1007/BF00169206. [DOI] [PubMed] [Google Scholar]
  30. Schoeffter P., Hoyer D. How selective is GR 43175? Interactions with functional 5-HT1A, 5-HT1B, 5-HT1C and 5-HT1D receptors. Naunyn Schmiedebergs Arch Pharmacol. 1989 Jul;340(1):135–138. doi: 10.1007/BF00169219. [DOI] [PubMed] [Google Scholar]
  31. Schoeffter P., Waeber C., Palacios J. M., Hoyer D. The 5-hydroxytryptamine 5-HT1D receptor subtype is negatively coupled to adenylate cyclase in calf substantia nigra. Naunyn Schmiedebergs Arch Pharmacol. 1988 Jun;337(6):602–608. doi: 10.1007/BF00175784. [DOI] [PubMed] [Google Scholar]
  32. Thomas R. F., Liggett S. B. Lack of beta 3-adrenergic receptor mRNA expression in adipose and other metabolic tissues in the adult human. Mol Pharmacol. 1993 Mar;43(3):343–348. [PubMed] [Google Scholar]
  33. Weinshank R. L., Zgombick J. M., Macchi M. J., Branchek T. A., Hartig P. R. Human serotonin 1D receptor is encoded by a subfamily of two distinct genes: 5-HT1D alpha and 5-HT1D beta. Proc Natl Acad Sci U S A. 1992 Apr 15;89(8):3630–3634. doi: 10.1073/pnas.89.8.3630. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Willett F., Curzen N., Adams J., Armitage M. Coronary vasospasm induced by subcutaneous sumatriptan. BMJ. 1992 May 30;304(6839):1415–1415. doi: 10.1136/bmj.304.6839.1415. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES