title: Angiotensin (1-7) prevents angiotensin II-induced nociceptive behaviour via inhibition of p38 MAPK phosphorylation mediated through spinal Mas receptors in mice.
abstract: BACKGROUND
  We have recently demonstrated that intrathecal (i.t.) administration of angiotensin II (Ang II) induces nociceptive behaviour in mice accompanied by a phosphorylation of p38 mitogen-activated protein kinase (MAPK) mediated through Ang II type 1 (AT1 ) receptors. The N-terminal fragment of Ang II, Ang (1-7), plays a pivotal role in counterbalancing many of the well-established actions induced by Ang II. However, the role of Ang (1-7) in spinal nociceptive transmission remains unclear. Therefore, we examined whether i.t. administration of Ang (1-7) can inhibit the Ang II-induced nociceptive behaviour in mice.
  
  
  METHODS
  In the behavioural experiments, the accumulated response time of nociceptive behaviour consisting of scratching, biting and licking in conscious mice was determined during a 25-min period starting after i.t. injection. The distribution and localization of AT1 or Mas receptors were analysed using a MapAnalyzer and confocal microscope, respectively. Phosphorylation of p38 MAPK in the dorsal spinal cord was measured by Western blotting.
  
  
  RESULTS
  The nociceptive behaviour induced by Ang II was dose-dependently inhibited by the co-administration of Ang (1-7). The inhibitory effect of Ang (1-7) was reversed by the co-administration of A779, a Mas receptor antagonist. Western blot analysis showed that the increase in spinal p38 MAPK phosphorylation following the i.t. administration of Ang II was also inhibited by Ang (1-7), and the Ang (1-7) induced-inhibition was prevented by A779.
  
  
  CONCLUSIONS
  Our data show that the i.t. administration of Ang (1-7) attenuates an Ang II-induced nociceptive behaviour and is accompanied by the inhibition of p38 MAPK phosphorylation mediated through Mas receptors.
authors.affiliation: Department of Pharmacology, Tohoku Pharmaceutical University, Sendai, Japan.
authors.forename: W
authors.initials: W
authors.lastname: Nemoto
authors.forename: Y
authors.initials: Y
authors.lastname: Ogata
authors.forename: O
authors.initials: O
authors.lastname: Nakagawasai
authors.forename: F
authors.initials: F
authors.lastname: Yaoita
authors.forename: T
authors.initials: T
authors.lastname: Tadano
authors.forename: K
authors.initials: K
authors.lastname: Tan-No
mesh_terms: D000803:Angiotensin I / Q000494:pharmacology*; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D007278:Injections, Spinal; D051379:Mice; D059226:Nociceptive Pain / Q000139:chemically induced / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D010766:Phosphorylation / Q000187:drug effects; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000187:drug effects* / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000187:drug effects* / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D048051:p38 Mitogen-Activated Protein Kinases / Q000187:drug effects* / Q000378:metabolism
chemical_list: D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D044140:Receptor, Angiotensin, Type 1; D043562:Receptors, G-Protein-Coupled; D000804:Angiotensin II; D000803:Angiotensin I; D048051:p38 Mitogen-Activated Protein Kinases; C118790:angiotensin I (1-7)