EXPRESSION CLONING OF A CDNA-ENCODING THE BOVINE HISTAMINE-H1 RECEPTOR

A functional cDNA clone for the histamine H-1 receptor was isolated from a cDNA library of bovine adrenal medulla by a combination of molecular cloning in an expression vector and electrophysiological assay in Xenopus oocytes. The H-1 receptor cDNA encodes a protein of 491 amino acids (M(r) 55,954) with seven putative transmembrane domains, illustrating the similarity to other receptors that couple with guanine nucleotide-binding regulatory proteins (G protein-coupled receptors). The sequence homology between the H-1 and H-2 receptors is not higher than that between the histamine H-1 and m1-muscarinic receptors. The cloned receptor protein expressed in COS-7 cells bound specifically to [H-3]mepyramine, an H-1 receptor antagonist, and this binding was displaced by H-1 receptor antagonists and histamine with affinities comparable with those in membranes of bovine adrenal medulla. H-1 receptor mRNA was shown to be expressed in brain and in peripheral tissues, including lung, small intestine, and adrenal medulla. This investigation discloses the molecular nature of the H-1 receptor-a receptor that mediates diverse neuronal and peripheral actions of histamine and that may be of therapeutic importance in allergy.