Molecular and functional characterization of a 5-HT4 receptor cloned from human atrium

FEBS Lett. 1997 Aug 4;412(3):465-74. doi: 10.1016/s0014-5793(97)00820-x.


5-Hydroxytryptamine (5-HT) has been shown to exert positive inotropic, chronotropic, and lusitropic effects and to stimulate the L-type calcium channel current (I(Ca)) in human atrial tissue through activation of the pharmacologically defined 5-HT4 receptor subtype. However, the molecular nature of the receptor(s) involved in these effects is still unknown. In the present study, we report the molecular nature of a 5-HT4 receptor cloned from human atrium, h5-HT4A. Sequence analysis reveals that h5-HT4A displays a 93% protein identity with the short form of the 5-HT4 receptor recently isolated from rat brain. h5-HT4A mRNA is expressed in human atrium but not ventricle, and is also found in brain and GI tract. h5-HT4A transiently expressed in COS-7 cells displays a classical 5-HT4 pharmacological profile. However, affinities of the h5-HT4A receptor for agonists such as ML10302, BIMU1, renzapride or zacopride were 4-10-fold lower than the ones found in brain. Moreover, the stimulatory patterns of cAMP formation by h5-HT4A in response to the 5-HT4 agonists ML10302 and renzapride were very similar to the patterns of stimulation of I(Ca) obtained in response to these compounds in human atrial myocytes. We conclude that h5-HT4A likely mediates the effects of 5-HT in human atrium and may differ from 5-HT4 receptor isoforms present in the brain and GI tract.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Amino Acid Sequence
  • Animals
  • Calcium Channels / drug effects
  • Child
  • Cloning, Molecular
  • Cyclic AMP / biosynthesis
  • Heart Atria / cytology
  • Heart Atria / drug effects
  • Heart Atria / metabolism*
  • Humans
  • Indoles
  • Kinetics
  • Middle Aged
  • Molecular Sequence Data
  • Myocardium / cytology
  • Myocardium / metabolism
  • Organ Specificity
  • Rats
  • Receptors, Serotonin / chemistry*
  • Receptors, Serotonin / genetics
  • Receptors, Serotonin / physiology*
  • Receptors, Serotonin, 5-HT4
  • Serotonin / pharmacology
  • Serotonin Antagonists / pharmacology
  • Serotonin Receptor Agonists / pharmacology
  • Sulfonamides


  • Calcium Channels
  • Indoles
  • Receptors, Serotonin
  • Serotonin Antagonists
  • Serotonin Receptor Agonists
  • Sulfonamides
  • Receptors, Serotonin, 5-HT4
  • Serotonin
  • Cyclic AMP
  • GR 113808

Associated data

  • GENBANK/U20907