title: Aliskiren reduces prorenin receptor expression and activity in cultured human aortic smooth muscle cells.
abstract: BACKGROUND
  The recent discovery of a specific receptor for renin/prorenin (PRR) has added new interest to the potential pharmacological actions of aliskiren, the first direct renin inhibitor.
  
  
  METHODS
  In the present study, to gain new insights into the pharmacological properties of aliskiren, we investigated the effect of aliskiren on PRR expression and activity in cultured human smooth muscle cells (HSMCs).
  
  
  RESULTS
  Co-incubation of HSMCs with angiotensinogen (ANG) (1.5 × 10(-7)M) and prorenin (10(-8)-10(-7)M) resulted in an efficient production (within 4h) of angiotensin I, almost completely inhibited by 10(-5)M aliskiren (-86.0 ± 14.0%). In HSMCs stimulated with both ANG and prorenin, a 24h incubation with aliskiren (10(-6)-10(-5)M) resulted in a concentration-dependent reduction of PRR mRNA levels (IC(50) 4.6 × 10(-6)M). The cell surface expression of PRR determined by flow cytometry analysis was also reduced after incubation with aliskiren in a concentration-dependent manner. The lower levels of PRR were associated with a reduced expression of TGF-β, PAI-1 and type I collagen mRNA.
  
  
  CONCLUSIONS
  These results suggest a direct pharmacological action of aliskiren on PRR expression and its signalling pathway in HSMCs. This reported action of aliskiren may reveal a new scenario of the pharmacological properties of aliskiren.
authors.affiliation: Department of Pharmacological Sciences, University of Milan, Italy. nicola.ferri@unimi.it
authors.forename: Nicola
authors.initials: N
authors.lastname: Ferri
authors.forename: Carolina Magdalen
authors.initials: CM
authors.lastname: Greco
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Maiocchi
authors.forename: Alberto
authors.initials: A
authors.lastname: Corsini
mesh_terms: D000577:Amides / Q000494:pharmacology*; D000803:Angiotensin I / Q000378:metabolism / Q000494:pharmacology; D000808:Angiotensinogen / Q000378:metabolism; D001011:Aorta / Q000166:cytology*; D002478:Cells, Cultured; D005650:Fumarates / Q000494:pharmacology*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D012083:Renin / Q000494:pharmacology; D000093342:Prorenin Receptor
chemical_list: D000577:Amides; D005650:Fumarates; D011956:Receptors, Cell Surface; D000808:Angiotensinogen; C446481:aliskiren; D000803:Angiotensin I; D012083:Renin; D000093342:Prorenin Receptor