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):408-12. doi: 10.1073/pnas.90.2.408.

Abstract

An intronless gene encoding an additional human serotonin (5-HT) 5-HT1-like receptor subtype was isolated from a human genomic library with probes obtained from degenerate PCR primers used to amplify 5-HT-receptor-specific sequences. The highest degree of homology was found with the 5-HT1E subtype (70%) and the 5-HT1D alpha (63%) and 5-HT1D beta (60%) receptors. RNA for this gene was detected in the human brain but was not detected in kidney, liver, spleen, heart, pancreas, and testes. High-affinity (Kd = 9.2 nM) 3H-labeled 5-HT binding was detected. Competition studies revealed the following rank order of potencies for serotonergic ligands: 5-HT > sumatriptan >> 5-carboxyamidotryptamine > 8-hydroxy-2(di-1-propylamino)tetralin > spiperone. 5-HT produced a dose-dependent inhibition of forskolin-stimulated cAMP accumulation (EC50 = 7.9 nM) in transfected cells. These properties distinguish this receptor from any previously characterized and establish a fifth 5-HT1-like receptor subtype (5-HT1F) coupled to the inhibition of adenylate cyclase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenylyl Cyclase Inhibitors
  • Adenylyl Cyclases / metabolism*
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Brain Chemistry
  • Cloning, Molecular
  • Colforsin / pharmacology
  • Dose-Response Relationship, Drug
  • Gene Library
  • Guinea Pigs
  • Humans
  • Indoles / pharmacology
  • Lymphocytes
  • Molecular Sequence Data
  • RNA, Messenger / isolation & purification
  • Receptors, Serotonin / classification
  • Receptors, Serotonin / genetics*
  • Sequence Homology, Amino Acid
  • Serotonin / analogs & derivatives
  • Serotonin / pharmacology
  • Serotonin Receptor Agonists / pharmacology*
  • Spiperone / pharmacology
  • Sulfonamides / pharmacology
  • Sumatriptan
  • Tissue Distribution

Substances

  • Adenylyl Cyclase Inhibitors
  • Indoles
  • RNA, Messenger
  • Receptors, Serotonin
  • Serotonin Receptor Agonists
  • Sulfonamides
  • Colforsin
  • Serotonin
  • Spiperone
  • Sumatriptan
  • 5-carboxamidotryptamine
  • Adenylyl Cyclases

Associated data

  • GENBANK/L04962