Cloning and pharmacological characterization of the monkey histamine H3 receptor.
Species differences have been described previously for histamine H(3) receptor pharmacology. Rat selective histamine H(3) receptor ligands such as ciproxifan and A-304121 (2-amino-1-[4-[3-(4-cyclopropanecarbonyl-phenoxy)-propyl]-piperazin-1-yl]-propan-1-one) show over 100-fold selectivity for the rat receptor compared to the human receptor. To date, however, the pharmacology of the cloned monkey histamine H(3) receptor has not been examined. In this study, we cloned the monkey histamine H(3) receptor gene (H(3)R) and evaluated the receptor pharmacology in binding and functional assays. The monkey histamine H(3) receptor is highly homologous to the human receptor with 438 identities in their 445 amino acid sequences, but less homologous to the rat receptor. However, unlike the human or rat, we found no evidence for additional splicing for the monkey H(3)R. Pharmacological analysis indicated that the monkey receptor exhibited similar pharmacological profiles to those of the human receptor, providing critical information for characterizing histamine H(3) receptor ligands in monkey behavioral models.
Yao
Betty Bei
BB
Neuroscience Research, Global Pharmaceutical Research & Development, Abbott Laboratories, R4MN, AP9A, 100 Abbott Park Road, Abbott Park, IL 60064, USA. betty.yao@abbott.com
Sharma
Rahul
R
Cassar
Steven
S
Esbenshade
Timothy A
TA
Hancock
Arthur A
AA
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D002460:Cell Line; D003001:Cloning, Molecular / Q000379:methods; D004305:Dose-Response Relationship, Drug; D017442:Histamine Agonists / Q000378:metabolism / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008253:Macaca mulatta / Q000235:genetics* / Q000378:metabolism*; D008969:Molecular Sequence Data; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018100:Receptors, Histamine H3 / Q000235:genetics* / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
D017442:Histamine Agonists; D006633:Histamine Antagonists; D020033:Protein Isoforms; D018100:Receptors, Histamine H3