title: Stimulation of histamine H1 receptor up-regulates histamine H1 receptor itself through activation of receptor gene transcription.
abstract: Histamine is a major mediator in allergy acting mainly through the histamine H(1) receptor (H1R). Although H1R up-regulation has been suggested as an important step for induction of allergic symptoms, little is known about the regulation of H1R level. Here we report that the activation of H1R up-regulates H1R through augmentation of H1R mRNA expression in HeLa cells. Histamine stimulation significantly increased both H1R promoter activity and mRNA level without alteration in mRNA stability. H1R protein was also up-regulated by histamine. An H1R antagonist but not histamine H(2) receptor antagonist blocked histamine-induced up-regulation of both promoter activity and mRNA expression. A protein kinase C (PKC) activator, phorbol-12-myristate-13-acetate, increased H1R mRNA expression, whereas an activator of PKA or PKG (8-Br-cAMP or 8-Br-cGMP, respectively) did not. Furthermore, histamine-induced up-regulation of both promoter activity and mRNA level were completely suppressed by the PKC inhibitor Ro-31-8220. H1R antagonists have long been thought to block H1R and inhibit immediate allergy symptoms. In addition to this short-term effect, our data propose their long-term inhibitory effect against allergic diseases by suppressing PKC-mediated H1R gene transcription. This finding provides new insights into the therapeutic target of H1R antagonist in allergic diseases.
authors.affiliation: Department of Molecular Pharmacology, Graduate School of Health Biosciences, The University of Tokushima, Japan.
authors.forename: Asish K
authors.initials: AK
authors.lastname: Das
authors.forename: Sachiho
authors.initials: S
authors.lastname: Yoshimura
authors.forename: Ryoko
authors.initials: R
authors.lastname: Mishima
authors.forename: Katsumi
authors.initials: K
authors.lastname: Fujimoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Mizuguchi
authors.forename: Shrabanti
authors.initials: S
authors.lastname: Dev
authors.forename: Yousuke
authors.initials: Y
authors.lastname: Wakayama
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kitamura
authors.forename: Shuhei
authors.initials: S
authors.lastname: Horio
authors.forename: Noriaki
authors.initials: N
authors.lastname: Takeda
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Fukui
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D002227:Carbazoles / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006367:HeLa Cells; D006632:Histamine / Q000494:pharmacology*; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D008156:Luciferases / Q000235:genetics / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011738:Pyrilamine / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011969:Receptors, Histamine H1 / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects*; D014162:Transfection; D014316:Tritium; D015854:Up-Regulation / Q000187:drug effects* / Q000235:genetics
chemical_list: D002227:Carbazoles; D004791:Enzyme Inhibitors; D006634:Histamine H1 Antagonists; D007211:Indoles; D011758:Pyrroles; D012333:RNA, Messenger; D011969:Receptors, Histamine H1; D013873:Thionucleotides; D014316:Tritium; C083763:8-bromoguanosino-3',5'-cyclic monophosphorothioate; D015124:8-Bromo Cyclic Adenosine Monophosphate; C057416:KT 5720; D006632:Histamine; D008156:Luciferases; D011493:Protein Kinase C; D006152:Cyclic GMP; D011738:Pyrilamine; D013755:Tetradecanoylphorbol Acetate; C064758:Ro 31-8220