Identification of histamine H_1 receptor subtypes

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mRNA derived from bovine adrenal medulla was fractionated by the sucrose density gradient centrifugation, and each fraction was injected into Xenopus Laevis oocytes. Expression of histamine H_1 receptors was electrophysiologically examined. Injection of fractions containing 3.5-kb mRNA or 5.0-kb mRNA induced the expression of histamine H_1 receptors. This result suggests the existence of histamine H_1 receptor subtypes. Histamine H_1 receptor-dependent inward Cl^- current was aprox. 50nA when 3.5-kb mRNA was injected, and smaller than 40nA when 5.0-kb mRNA was injected. cDNA libraries derived from 3.5-kb mRMA and 5.0-kb mRNA were constructed using lambda ZAPII,a vector for in vitro transcription. The cDNA library was screened by the injection of mRNA through in vitro transcription and electrophysiological detection of histamine H_1 receptor expression. The histamine H_1 receptor cDNA derived from 3.5-kb mRNA was isolated, and the structure of the receptor was determined. The detection of histamine H_1 receptor-dependent inward Cl^- current from 5.0-kb mRNA fraction was not succeeded when mRNA through in vitro transcription was injected. Recently histamine H_1 receptor knock out mouse was prepared, and the lack of histamine H_1 receptors was demonstrated by the autoradiography of [^3H] mepyramine binding. This result indicated that mouse has only one histamine H_1 receptor gene. We observed that human and guinea pig have two kinds of histamine H_1 rceptor mRNAs with different molecular weights. Physiological and pathological roles of histamine differ from species, and the possibility of histamine H_1 receptor subtypes in human and guinea pig still remains.