Molecular cloning and characterization of a new human histamine receptor, HH4R.
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.
Nakamura
T
T
Banyu Pharmaceutical Company, Ltd., Tsukuba Research Institute, Okubo 3, Tsukuba, Ibaraki, 300-2611, Japan.
Itadani
H
H
Hidaka
Y
Y
Ohta
M
M
Tanaka
K
K
D000595:Amino Acid Sequence; D001667:Binding, Competitive; D002460:Cell Line; D002927:Cimetidine / Q000494:pharmacology; D003001:Cloning, Molecular; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D017442:Histamine Agonists / Q000493:pharmacokinetics / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology*; D006801:Humans; D007962:Leukocytes / Q000502:physiology; D008761:Methylhistamines / Q000493:pharmacokinetics / Q000494:pharmacology; D008969:Molecular Sequence Data; D011738:Pyrilamine / Q000494:pharmacology; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D018100:Receptors, Histamine H3 / Q000737:chemistry / Q000235:genetics; D000074040:Receptors, Histamine H4; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013237:Stereoisomerism; D014162:Transfection
C418607:HRH4 protein, human; D017442:Histamine Agonists; D006633:Histamine Antagonists; D008761:Methylhistamines; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D018100:Receptors, Histamine H3; D000074040:Receptors, Histamine H4; D011994:Recombinant Proteins; D005576:Colforsin; C069357:alpha-methylhistamine; D002927:Cimetidine; D000242:Cyclic AMP; D011738:Pyrilamine