RT Journal Article
SR Electronic
T1 Cloning and Characterization of a Novel Human Histamine Receptor
JF Journal of Pharmacology and Experimental Therapeutics
JO J Pharmacol Exp Ther
FD American Society for Pharmacology and Experimental Therapeutics
SP 1058
OP 1066
VO 296
IS 3
A1 Kelley L. Morse
A1 Jiang Behan
A1 Thomas M. Laz
A1 Robert E. West, Jr.
A1 Scott A. Greenfeder
A1 John C. Anthes
A1 Shelby Umland
A1 Yuntao Wan
A1 R. William Hipkin
A1 Waldemar Gonsiorek
A1 Niu Shin
A1 Eric L. Gustafson
A1 Xudong Qiao
A1 Suke Wang
A1 Joseph A. Hedrick
A1 Jonathan Greene
A1 Marvin Bayne
A1 Frederick J. Monsma, Jr.
YR 2001
UL http://jpet.aspetjournals.org/content/296/3/1058.abstract
AB Histamine exerts its numerous physiological functions through interaction with G protein-coupled receptors. Three such receptors have been defined at both the pharmacological and molecular level, while pharmacological evidence hints at the existence of further subtypes. We report here the cloning and characterization of a fourth histamine receptor subtype. Initially discovered in an expressed-sequence tag database, the full coding sequence (SP9144) was subsequently identified in chromosome 18 genomic sequence. This virtual coding sequence exhibited highest homology to the H3histamine receptor and was used to generate a full-length clone by polymerase chain reaction (PCR). The distribution of mRNA encoding SP9144 was restricted to cells of the immune system as determined by quantitative PCR. HEK-293 cells transiently transfected with SP9144 and a chimeric G protein α-subunit (Gαq/i1,2) exhibited increases in intracellular [Ca2+] in response to histamine but not other biogenic amines. SP9144-transfected cells exhibited saturable, specific, high-affinity binding of [3H]histamine, which was potently inhibited by H3 receptor-selective compounds. The rank order and potency of these compounds at SP9144 differed from the rank order at the H3 receptor. Although SP9144 apparently coupled to Gαi, HEK-293 cells stably transfected with SP9144 did not exhibit histamine-mediated inhibition of forskolin-stimulated cAMP levels. However, both [35S]GTPγS binding and phosphorylation of mitogen-activated protein kinase were stimulated by histamine via SP9144 activation. In both of these assays, SP9144 exhibited evidence of constitutive activation. Taken together, these data demonstrate that SP9144 is a unique, fourth histamine receptor subtype. The American Society for Pharmacology and Experimental Therapeutics