Expression Cloning of a CDNA Encoding the Bovine Histamine H1 Receptor

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1991 Dec 15

PMID 1722337

Citations 38

Authors

M Yamashita

H Fukui

K Sugama

Y Horio

S Ito

H Mizuguchi

H Wada

Affiliations

Soon will be listed here.

Abstract

A functional cDNA clone for the histamine H1 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 H1 receptor cDNA encodes a protein of 491 amino acids (Mr 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 H1 and H2 receptors is not higher than that between the histamine H1 and m1-muscarinic receptors. The cloned receptor protein expressed in COS-7 cells bound specifically to [3H]mepyramine, an H1 receptor antagonist, and this binding was displaced by H1 receptor antagonists and histamine with affinities comparable with those in membranes of bovine adrenal medulla. H1 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 H1 receptor--a receptor that mediates diverse neuronal and peripheral actions of histamine and that may be of therapeutic importance in allergy.

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