title: A search for functional histamine H4 receptors in the human, guinea pig and mouse brain.
abstract: Histamine H4 receptors are expressed in immune cells, but their potential role in the brain is less clear. Although H4 transcripts have been identified in human and rat brain, the presence of H4 receptors on the protein level has so far not been proven since appropriate antibodies fulfilling the strict criteria for G protein-coupled receptors are missing. Here, we searched for functional H4 receptors in human, guinea pig and mouse cortex. We studied whether H4 receptor activation is associated with increased GTPγS binding and reduced noradrenaline release. The latter two effects have been previously shown for H3 receptors, which, like the H4 receptors, are coupled to G i/o protein. G protein activation was studied using (35)S-GTPγS binding in cortical membranes. The electrically induced (3)H-noradrenaline release was determined in superfused cortical slices. The H4 agonist 4-methylhistamine failed to affect (35)S-GTPγS binding and/or noradrenaline release in human, guinea pig and mouse cortex although an H 3 receptor-mediated increase in (35)S-GTPγS binding and inhibition of noradrenaline release occurred in parallel experiments. In conclusion, functional H4 receptors increasing (35)S-GTPγS binding and/or decreasing noradrenaline release are not found in human, guinea pig and mouse cortex.
authors.affiliation: Institut für Pharmakologie und Toxikologie, Universität Bonn, Sigmund-Freud-Str. 25, 53105, Bonn, Germany.
authors.forename: Monika
authors.initials: M
authors.lastname: Feliszek
authors.forename: Valerie
authors.initials: V
authors.lastname: Speckmann
authors.forename: Daniel
authors.initials: D
authors.lastname: Schacht
authors.forename: Marec
authors.initials: M
authors.lastname: von Lehe
authors.forename: Holger
authors.initials: H
authors.lastname: Stark
authors.forename: Eberhard
authors.initials: E
authors.lastname: Schlicker
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D002648:Child; D005260:Female; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D017442:Histamine Agonists / Q000494:pharmacology; D006801:Humans; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009638:Norepinephrine / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000378:metabolism*; D011968:Receptors, Histamine / Q000378:metabolism*; D018100:Receptors, Histamine H3 / Q000378:metabolism; D000074040:Receptors, Histamine H4; D055815:Young Adult
chemical_list: C418607:HRH4 protein, human; D017442:Histamine Agonists; C498829:Hrh4 protein, mouse; D008761:Methylhistamines; D043562:Receptors, G-Protein-Coupled; D011968:Receptors, Histamine; D018100:Receptors, Histamine H3; D000074040:Receptors, Histamine H4; D016244:Guanosine 5'-O-(3-Thiotriphosphate); C025566:4-methylhistamine; D006632:Histamine; D009638:Norepinephrine