title: Identification of histamine receptor subtypes in skeletal myogenesis.
abstract: To date, conventional and/or novel histamine receptors (HRs) have not been investigated in mouse skeletal myogenesis. Therefore, the present study aimed to investigate the HR‑subtypes in skeletal myogenesis. The myogenesis of C2C12 skeletal myoblasts was evaluated using desmin, myogenin and myosin heavy chain (Myh) as early, intermediate and late differentiation markers, respectively. Reverse transcription‑quantitative polymerase chain reaction and immunostaining were performed and the messenger RNA (mRNA) expression levels of the HR‑subtypes and markers were determined. H1R mRNA was found to be highly expressed in myoblasts at day 0; however, the expression levels were reduced as differentiation progressed. By contrast, H2R mRNA expression remained constant, while H3R mRNA expression increased by 28‑, 103‑ and 198‑fold at days 2, 4 and 6 compared with the baseline level (day 0), respectively. In addition, Myh expression increased by 7,718‑, 94,487‑ and 286,288‑fold on days 2, 4 and 6 compared with the baseline expression level (day 0). Weak positive staining of the cells for H3R protein was observed on day 2, whereas highly positive staining was observed on days 4 and 6. HR expression during myogenesis was, in part, regulated by the stage of differentiation. These results along with previous findings indicated possible involvement of H1R in the regulation of progenitor cell mitogenesis and of H2R in the relaxation of acetylcholine‑stimulated contraction of muscle cells, following the activation of professional histamine‑producing cells, including mast cells. By contrast, H3R may participate in the regulation of specialized myocyte functions, potentially by maintaining the relaxed state under the influence of constitutive H3R activity and low histamine concentrations, locally produced/released by non‑professional histamine‑producing cells.
authors.affiliation: Department of Medicine, Institute of Clinical Medicine, University of Helsinki, Biomedicum 1, Helsinki 00029, Finland.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Medicine, Institute of Clinical Medicine, University of Helsinki, Biomedicum 1, Helsinki 00029, Finland.
authors.forename: Vasily
authors.initials: V
authors.lastname: Stegaev
authors.affiliation: Department of Medicine, Institute of Clinical Medicine, University of Helsinki, Biomedicum 1, Helsinki 00029, Finland.
authors.forename: Vesa-Petteri
authors.initials: VP
authors.lastname: Kouri
authors.affiliation: Department of Medicine, Institute of Clinical Medicine, University of Helsinki, Biomedicum 1, Helsinki 00029, Finland.
authors.forename: Tarvo
authors.initials: T
authors.lastname: Sillat
authors.affiliation: School of Biological and Biomedical Sciences, Durham University, Durham DH1 3LE, UK.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Chazot
authors.affiliation: Institute of Pharmaceutical Chemistry, Goethe University, Frankfurt D‑60438, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Stark
authors.affiliation: Department of Urology, Pediatric Urodynamic Center, Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, P.R. China.
authors.forename: Jian Guo
authors.initials: JG
authors.lastname: Wen
authors.affiliation: Department of Medicine, Institute of Clinical Medicine, University of Helsinki, Biomedicum 1, Helsinki 00029, Finland.
authors.forename: Yrjö T
authors.initials: YT
authors.lastname: Konttinen
mesh_terms: D000818:Animals; D002460:Cell Line; D015870:Gene Expression; D007150:Immunohistochemistry; D051379:Mice; D024510:Muscle Development / Q000235:genetics*; D018482:Muscle, Skeletal / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011968:Receptors, Histamine / Q000235:genetics* / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D011968:Receptors, Histamine