Molecular and pharmacological characterization of the mouse histamine H3 receptor.
Human, guinea pig and rat histamine H(3) receptors have been investigated at both pharmacological and molecular levels in recent years. Here we report the cloning, molecular, and pharmacological characterization of the mouse histamine H(3) receptor. The amino acid sequence of the mouse histamine H(3) receptor exhibits high homology to rat, guinea pig and human histamine H(3) receptors with 98%, 95%, 94% identities, respectively. The distribution of the mRNA encoding the mouse histamine H(3) receptor was predominant in the brain as detected by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and RNase protection assay. Although several splice forms have been reported for human, guinea pig and rat histamine H(3) receptor mRNAs, we did not detect equivalent isoforms in the mouse in several tissues by either RNase protection assay or robust Polymerase Chain Reaction (PCR) amplifications. Human embryonic kidney (HEK)-293 cells transiently transfected with mouse histamine H(3) receptor cDNA and Gq(i5) exhibited increases of intracellular Ca(2+) in response to histamine and several histamine H(3) receptor agonists. COS-7 (African green monkey kidney) cells transfected with mouse histamine H(3) receptor cDNA showed high affinity binding for histamine H(3) receptor ligands in competition binding assays. The pharmacological comparison of human, guinea pig, rat and mouse histamine H(3) receptors indicated that, as expected, the mouse histamine H(3) receptor exhibited a more similar pharmacological profile to the rat histamine H(3) receptor than to either the human or the guinea pig histamine H(3) receptor. Taken together, these findings allow a further appreciation of the histamine H(3) receptor at the molecular level and provide an additional species to assist in the pharmacological assessment of histamine H(3) receptor function.
Chen
Jingcai
J
Johnson & Johnson Pharmaceutical Research and Development, 3210 Merryfield Row, San Diego, CA 92121, USA.
Liu
Changlu
C
Lovenberg
Timothy W
TW
D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D003001:Cloning, Molecular; D006168:Guinea Pigs; D006632:Histamine / Q000378:metabolism; D017442:Histamine Agonists / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D051379:Mice; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D018100:Receptors, Histamine H3 / Q000187:drug effects / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017385:Sequence Homology; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology
D017442:Histamine Agonists; D006633:Histamine Antagonists; D007093:Imidazoles; D012333:RNA, Messenger; D018100:Receptors, Histamine H3; D006632:Histamine; D013890:Thiourea; C086108:clobenpropit; D002118:Calcium