title: Adrenomedullin-induced relaxation of rat brain pericytes is related to the reduced phosphorylation of myosin light chain through the cAMP/PKA signaling pathway.
abstract: Brain pericytes are known to embrace the abluminal endothelial surfaces of cerebral microvessels. The rich expression of contractile proteins in these cells suggests pericytal regulation of cerebral blood flow. Here, we investigated the molecular mechanisms by which an endothelium-derived relaxing factor, adrenomedullin, was able to induce the relaxation of rat primary cultured brain pericytes. Adrenomedullin increased the relative proportion of pericytes that were relaxed, as shown by an increased cell surface area. A smaller fragment of adrenomedullin (adrenomedullin(22-52)) blocked the adrenomedullin-induced relaxation. Adrenomedullin increased intracellular cAMP concentrations and decreased the phosphorylation of myosin light chain (MLC). H89 (a PKA inhibitor) inhibited the adrenomedullin-induced increase in the number of relaxed pericytes, and returned the level of phosphorylation of MLC to the control level. The results of the present study suggest that adrenomedullin-induced relaxation of brain pericytes is related to the reduced phosphorylation of MLC through cAMP/PKA.
authors.affiliation: Department of Pharmaceutical Care and Health Sciences, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan.
authors.forename: Fuyuko
authors.initials: F
authors.lastname: Takata
authors.forename: Shinya
authors.initials: S
authors.lastname: Dohgu
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Nishioku
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Eriko
authors.initials: E
authors.lastname: Harada
authors.forename: Ikuko
authors.initials: I
authors.lastname: Makino
authors.forename: Manabu
authors.initials: M
authors.lastname: Nakashima
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamauchi
authors.forename: Yasufumi
authors.initials: Y
authors.lastname: Kataoka
mesh_terms: D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone / Q000494:pharmacology; D053607:Adrenomedullin / Q000494:pharmacology*; D000818:Animals; D001921:Brain / Q000166:cytology*; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism* / Q000494:pharmacology; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D018994:Myosin Light Chains / Q000378:metabolism*; D020286:Pericytes / Q000187:drug effects* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013449:Sulfonamides / Q000494:pharmacology; D013997:Time Factors; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D007546:Isoquinolines; D018994:Myosin Light Chains; D013449:Sulfonamides; D014665:Vasodilator Agents; D053607:Adrenomedullin; D012368:4-(3-Butoxy-4-methoxybenzyl)-2-imidazolidinone; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide