Molecular cloning and characterization of a new human histamine receptor, HH4R

Biochem Biophys Res Commun. 2000 Dec 20;279(2):615-20. doi: 10.1006/bbrc.2000.4008.

Abstract

A new histamine receptor, HH4R, was cloned from human leukocyte cDNA. The deduced amino acid sequence showed about 40% identity to that of the human histamine H3 receptor, HH3R. HH4R-expressing cells responded to histamine, inhibiting forskolin-induced cAMP accumulation. An H3 agonist, N-alpha-methylhistamine (NAMHA), bound specifically to HH4R, while another H3 agonist, R(-)-alpha-methylhistamine (RAMHA), and the H3 antagonist, thioperamide, competed with this binding. RAMHA, NAMHA, and imetit inhibited forskolin-induced cAMP accumulation in HH4R-expressing cells. However, the binding affinities and agonistic activities of H3 agonists to HH4R were weaker than those to HH3R. Low expression of HH4R was detected in a wide variety of peripheral tissues by RT-PCR; however, in contrast with HH3R, expression was not detected in the brain. These observations indicate that the clone is a distinct histamine receptor from HH3R, and thus is named HH4R.

MeSH terms

  • Amino Acid Sequence
  • Binding, Competitive
  • Cell Line
  • Cimetidine / pharmacology
  • Cloning, Molecular
  • Colforsin / pharmacology
  • Cyclic AMP / metabolism
  • Histamine Agonists / pharmacokinetics
  • Histamine Agonists / pharmacology*
  • Histamine Antagonists / pharmacology*
  • Humans
  • Leukocytes / physiology
  • Methylhistamines / pharmacokinetics
  • Methylhistamines / pharmacology
  • Molecular Sequence Data
  • Pyrilamine / pharmacology
  • Receptors, G-Protein-Coupled*
  • Receptors, Histamine / chemistry
  • Receptors, Histamine / genetics
  • Receptors, Histamine / physiology*
  • Receptors, Histamine H3 / chemistry
  • Receptors, Histamine H3 / genetics
  • Receptors, Histamine H4
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / metabolism
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Stereoisomerism
  • Transfection

Substances

  • HRH4 protein, human
  • Histamine Agonists
  • Histamine Antagonists
  • Methylhistamines
  • Receptors, G-Protein-Coupled
  • Receptors, Histamine
  • Receptors, Histamine H3
  • Receptors, Histamine H4
  • Recombinant Proteins
  • Colforsin
  • alpha-methylhistamine
  • Cimetidine
  • Cyclic AMP
  • Pyrilamine