STABLE EXPRESSION OF HUMAN H-1-HISTAMINE-RECEPTOR CDNA IN CHINESE-HAMSTER OVARY CELLS - PHARMACOLOGICAL CHARACTERIZATION OF THE PROTEIN, TISSUE DISTRIBUTION OF MESSENGER-RNA AND CHROMOSOMAL LOCALIZATION OF THEGENE

A cDNA clone for the histamine H-1, receptor was isolated from a human lung cDNA library; it encoded a protein of 487 amino acids which show ed characteristic features of G-protein-coupled receptors. The percent ages of identity of the deduced amino acid sequence with bovine, rat a nd guinea pig H-1 histamine receptors were 82.6%, 79.4% and 73.3%, res pectively, whereas these percentages decreased to 74.6%, 66% and 56.7% for the amino acid sequence of the third intracellular loop. The huma n H-1-receptor cDNA was transfected into Chinese hamster ovary cells ( CHO) via an eukaryotic expression vector; the receptor protein present on cell membranes specifically bound [H-3]mepyramine with a K-d of 3. 7 nM. The binding was displaced by H-1-histamine-receptor antagonists and histamine. Northern blot analysis indicated the presence of two hi stamine H-1 receptor mRNAs of 3.5 kb and 4.1 kb in various human tissu es and an additional mRNA of 4.8 kb restricted to the human brain. Fin ally, by means of somatic cell hybrids segregating either human or rat chromosomes, the gene for histamine H-1 receptor was found to reside on human chromosome 3 and rat chromosome 4.