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.
Copyright 2000 Academic Press.
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