MOLECULAR-CLONING OF THE GUINEA-PIG HISTAMINE-H-1 RECEPTOR GENE

The histamine H-1 receptor gene was isolated from a guinea-pig gene library. The gene contains no introns and encodes a protein of 488 amino acid residues. The structure of the guinea-pig histamine H-1 receptor is predicted to contain seven putative transmembrane regions, which are similar to those of receptors coupling with GTP binding proteins. Although the third intracellular domain, the predicted binding site for the GTP binding protein, showed only 50% identity with those of the bovine and rat H-1 receptors, the expressed guinea-pig H-1 receptor was fully ab le to bind with [H-3] mepyramine. Northern blot analysis indicated that the cerebrum, cerebellum, lung, adrenal, intestine, and heart expressed 3.3 kb guinea-pig H-1 receptor mRNA. Expression of histamine H-1 mRNA of guinea-pig peripheral organs was greater than that of rat organs, suggesting the high sensitivity of guinea-pig organs as to histamine is due to the contents of histamine H-1 receptor mRNA. In addition, the lung, adrenal, intestine, and heart expressed 3.9 kb mRNA. In situ hybridization showed that the hippocampus, cerebral cortex, thalamus, and granular layer of the cerebellum each contained a large amount of histamine H-1 receptors. Southern blot analysis showed that there was another gene quite similar to the cloned histamine H-1 receptor gene.