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. 1992 Dec;11(13):4779–4786. doi: 10.1002/j.1460-2075.1992.tb05583.x

The mouse 5HT5 receptor reveals a remarkable heterogeneity within the 5HT1D receptor family.

J L Plassat 1, U Boschert 1, N Amlaiky 1, R Hen 1
PMCID: PMC556953  PMID: 1464308

Abstract

Serotonin (5-HT) is a neuromodulator that mediates a wide range of physiological functions by activating multiple receptors. Using a strategy based on amino acid sequence homology between 5-HT receptors that interact with G proteins, we have isolated a cDNA encoding a new serotonin receptor from a mouse brain library. Amino acid sequence comparisons revealed that this receptor was a distant relative of all previously identified 5-HT receptors; we therefore named it 5HT5. When expressed in Cos-7 cells and NIH-3T3 cells, the 5HT5 receptor displayed a high affinity for the serotonergic radioligand [125I]LSD. Surprisingly, its pharmacological profile resembled that of the 5HT1D receptor, which is a 5-HT receptor subtype which has been shown to inhibit adenylate cyclase and which is predominantly expressed in basal ganglia. However, unlike 5HT1D receptors, the 5HT5 receptor did not inhibit adenylate cyclase and its mRNA was not found in basal ganglia. On the contrary, in situ hybridization experiments revealed that the 5HT5 mRNA was expressed predominantly in cerebral cortex, hippocampus, habenula, olfactory bulb and granular layer of the cerebellum. Our results therefore demonstrate that the 5HT1D receptors constitute a heterogeneous family of receptors with distinct intracellular signalling properties and expression patterns.

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Selected References

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  1. Adham N., Romanienko P., Hartig P., Weinshank R. L., Branchek T. The rat 5-hydroxytryptamine1B receptor is the species homologue of the human 5-hydroxytryptamine1D beta receptor. Mol Pharmacol. 1992 Jan;41(1):1–7. [PubMed] [Google Scholar]
  2. Amlaiky N., Caron M. G. Photoaffinity labeling of the D2-dopamine receptor using a novel high affinity radioiodinated probe. J Biol Chem. 1985 Feb 25;260(4):1983–1986. [PubMed] [Google Scholar]
  3. Asarch K. B., Ransom R. W., Shih J. C. 5-HT-1a and 5-HT-1b selectivity of two phenylpiperazine derivatives: evidence for 5-HT-1b heterogeneity. Life Sci. 1985 Apr 1;36(13):1265–1273. doi: 10.1016/0024-3205(85)90271-1. [DOI] [PubMed] [Google Scholar]
  4. Beer M. S., Stanton J. A., Bevan Y., Chauhan N. S., Middlemiss D. N. An investigation of the 5-HT1D receptor binding affinity of 5-hydroxytryptamine, 5-carboxyamidotryptamine and sumatriptan in the central nervous system of seven species. Eur J Pharmacol. 1992 Mar 24;213(2):193–197. doi: 10.1016/0014-2999(92)90681-s. [DOI] [PubMed] [Google Scholar]
  5. Bouhelal R., Smounya L., Bockaert J. 5-HT1B receptors are negatively coupled with adenylate cyclase in rat substantia nigra. Eur J Pharmacol. 1988 Jul 7;151(2):189–196. doi: 10.1016/0014-2999(88)90799-6. [DOI] [PubMed] [Google Scholar]
  6. Bunzow J. R., Van Tol H. H., Grandy D. K., Albert P., Salon J., Christie M., Machida C. A., Neve K. A., Civelli O. Cloning and expression of a rat D2 dopamine receptor cDNA. Nature. 1988 Dec 22;336(6201):783–787. doi: 10.1038/336783a0. [DOI] [PubMed] [Google Scholar]
  7. Colino A., Halliwell J. V. Differential modulation of three separate K-conductances in hippocampal CA1 neurons by serotonin. Nature. 1987 Jul 2;328(6125):73–77. doi: 10.1038/328073a0. [DOI] [PubMed] [Google Scholar]
  8. Conn P. J., Sanders-Bush E. Serotonin-stimulated phosphoinositide turnover: mediation by the S2 binding site in rat cerebral cortex but not in subcortical regions. J Pharmacol Exp Ther. 1985 Jul;234(1):195–203. [PubMed] [Google Scholar]
  9. De Lean A., Kilpatrick B. F., Caron M. G. Dopamine receptor of the porcine anterior pituitary gland. Evidence for two affinity states discriminated by both agonists and antagonists. Mol Pharmacol. 1982 Sep;22(2):290–297. [PubMed] [Google Scholar]
  10. Dearry A., Gingrich J. A., Falardeau P., Fremeau R. T., Jr, Bates M. D., Caron M. G. Molecular cloning and expression of the gene for a human D1 dopamine receptor. Nature. 1990 Sep 6;347(6288):72–76. doi: 10.1038/347072a0. [DOI] [PubMed] [Google Scholar]
  11. Fargin A., Raymond J. R., Lohse M. J., Kobilka B. K., Caron M. G., Lefkowitz R. J. The genomic clone G-21 which resembles a beta-adrenergic receptor sequence encodes the 5-HT1A receptor. Nature. 1988 Sep 22;335(6188):358–360. doi: 10.1038/335358a0. [DOI] [PubMed] [Google Scholar]
  12. Frielle T., Collins S., Daniel K. W., Caron M. G., Lefkowitz R. J., Kobilka B. K. Cloning of the cDNA for the human beta 1-adrenergic receptor. Proc Natl Acad Sci U S A. 1987 Nov;84(22):7920–7924. doi: 10.1073/pnas.84.22.7920. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gantz I., Schäffer M., DelValle J., Logsdon C., Campbell V., Uhler M., Yamada T. Molecular cloning of a gene encoding the histamine H2 receptor. Proc Natl Acad Sci U S A. 1991 Jan 15;88(2):429–433. doi: 10.1073/pnas.88.2.429. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Green S., Issemann I., Sheer E. A versatile in vivo and in vitro eukaryotic expression vector for protein engineering. Nucleic Acids Res. 1988 Jan 11;16(1):369–369. doi: 10.1093/nar/16.1.369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hafen E., Levine M., Garber R. L., Gehring W. J. An improved in situ hybridization method for the detection of cellular RNAs in Drosophila tissue sections and its application for localizing transcripts of the homeotic Antennapedia gene complex. EMBO J. 1983;2(4):617–623. doi: 10.1002/j.1460-2075.1983.tb01472.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. 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]
  17. Hen R. Of mice and flies: commonalities among 5-HT receptors. Trends Pharmacol Sci. 1992 Apr;13(4):160–165. doi: 10.1016/0165-6147(92)90054-a. [DOI] [PubMed] [Google Scholar]
  18. Herrick-Davis K., Titeler M. Detection and characterization of the serotonin 5-HT 1D receptor in rat and human brain. J Neurochem. 1988 May;50(5):1624–1631. doi: 10.1111/j.1471-4159.1988.tb03052.x. [DOI] [PubMed] [Google Scholar]
  19. Herrick-Davis K., Titeler M., Leonhardt S., Struble R., Price D. Serotonin 5-HT1D receptors in human prefrontal cortex and caudate: interaction with a GTP binding protein. J Neurochem. 1988 Dec;51(6):1906–1912. doi: 10.1111/j.1471-4159.1988.tb01176.x. [DOI] [PubMed] [Google Scholar]
  20. Heuring R. E., Schlegel J. R., Peroutka S. J. Species variations in RU 24969 interactions with non-5-HT1A binding sites. Eur J Pharmacol. 1986 Mar 18;122(2):279–282. doi: 10.1016/0014-2999(86)90114-7. [DOI] [PubMed] [Google Scholar]
  21. Higgins D. G., Sharp P. M. CLUSTAL: a package for performing multiple sequence alignment on a microcomputer. Gene. 1988 Dec 15;73(1):237–244. doi: 10.1016/0378-1119(88)90330-7. [DOI] [PubMed] [Google Scholar]
  22. Julius D., MacDermott A. B., Axel R., Jessell T. M. Molecular characterization of a functional cDNA encoding the serotonin 1c receptor. Science. 1988 Jul 29;241(4865):558–564. doi: 10.1126/science.3399891. [DOI] [PubMed] [Google Scholar]
  23. Julius D. Molecular biology of serotonin receptors. Annu Rev Neurosci. 1991;14:335–360. doi: 10.1146/annurev.ne.14.030191.002003. [DOI] [PubMed] [Google Scholar]
  24. Kobilka B. K., Matsui H., Kobilka T. S., Yang-Feng T. L., Francke U., Caron M. G., Lefkowitz R. J., Regan J. W. Cloning, sequencing, and expression of the gene coding for the human platelet alpha 2-adrenergic receptor. Science. 1987 Oct 30;238(4827):650–656. doi: 10.1126/science.2823383. [DOI] [PubMed] [Google Scholar]
  25. Leonhardt S., Herrick-Davis K., Titeler M. Detection of a novel serotonin receptor subtype (5-HT1E) in human brain: interaction with a GTP-binding protein. J Neurochem. 1989 Aug;53(2):465–471. doi: 10.1111/j.1471-4159.1989.tb07357.x. [DOI] [PubMed] [Google Scholar]
  26. Mahle C. D., Nowak H. P., Mattson R. J., Hurt S. D., Yocca F. D. [3H]5-carboxamidotryptamine labels multiple high affinity 5-HT1D-like sites in guinea pig brain. Eur J Pharmacol. 1991 Dec 3;205(3):323–324. doi: 10.1016/0014-2999(91)90919-h. [DOI] [PubMed] [Google Scholar]
  27. Maroteaux L., Saudou F., Amlaiky N., Boschert U., Plassat J. L., Hen R. Mouse 5HT1B serotonin receptor: cloning, functional expression, and localization in motor control centers. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3020–3024. doi: 10.1073/pnas.89.7.3020. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Peroutka S. J. Cortical and striatal variations in drug competition studies with putative 5-hydroxytryptamine1D binding sites. Brain Res. 1991 Jul 12;553(2):206–210. doi: 10.1016/0006-8993(91)90826-h. [DOI] [PubMed] [Google Scholar]
  29. Pritchett D. B., Bach A. W., Wozny M., Taleb O., Dal Toso R., Shih J. C., Seeburg P. H. Structure and functional expression of cloned rat serotonin 5HT-2 receptor. EMBO J. 1988 Dec 20;7(13):4135–4140. doi: 10.1002/j.1460-2075.1988.tb03308.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Raiteri M., Maura G., Bonanno G., Pittaluga A. Differential pharmacology and function of two 5-HT1 receptors modulating transmitter release in rat cerebellum. J Pharmacol Exp Ther. 1986 May;237(2):644–648. [PubMed] [Google Scholar]
  31. Saudou F., Boschert U., Amlaiky N., Plassat J. L., Hen R. A family of Drosophila serotonin receptors with distinct intracellular signalling properties and expression patterns. EMBO J. 1992 Jan;11(1):7–17. doi: 10.1002/j.1460-2075.1992.tb05021.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Schoeffter P., Hoyer D. 5-Hydroxytryptamine 5-HT1B and 5-HT1D receptors mediating inhibition of adenylate cyclase activity. Pharmacological comparison with special reference to the effects of yohimbine, rauwolscine and some beta-adrenoceptor antagonists. Naunyn Schmiedebergs Arch Pharmacol. 1989 Sep;340(3):285–292. doi: 10.1007/BF00168512. [DOI] [PubMed] [Google Scholar]
  33. Sumner M. J., Humphrey P. P. 5-HT1D binding sites in porcine brain can be sub-divided by GR43175. Br J Pharmacol. 1989 Sep;98(1):29–31. doi: 10.1111/j.1476-5381.1989.tb16856.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Voigt M. M., Laurie D. J., Seeburg P. H., Bach A. Molecular cloning and characterization of a rat brain cDNA encoding a 5-hydroxytryptamine1B receptor. EMBO J. 1991 Dec;10(13):4017–4023. doi: 10.1002/j.1460-2075.1991.tb04977.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Waeber C., Schoeffter P., Hoyer D., Palacios J. M. The serotonin 5-HT1D receptor: a progress review. Neurochem Res. 1990 Jun;15(6):567–582. doi: 10.1007/BF00973745. [DOI] [PubMed] [Google Scholar]
  36. 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]
  37. Yakel J. L., Trussell L. O., Jackson M. B. Three serotonin responses in cultured mouse hippocampal and striatal neurons. J Neurosci. 1988 Apr;8(4):1273–1285. doi: 10.1523/JNEUROSCI.08-04-01273.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]

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