title: Targeting sigma-1 receptor signaling by endogenous ligands for cardioprotection.
abstract: BACKGROUND
  The sigma receptors, initially described as a subtype of opioid receptors, are now considered to be a unique receptor expressed in neonatal rat cardiomyocytes and in the plasma membrane of adult rat cardiomyocytes. A number of sigma receptor ligands influence cardiovascular function and the heart has binding sites for sigma receptor ligands that alter contractility both in vivo and in vitro. The human sigma-1 receptor gene contains a steroid-binding component and gonadal steroid dehydroepiandrosterone (DHEA) which interacts with the sigma-1 receptor.
  
  
  METHODS
  We recently documented that the pathophysiological role of the sigma-1 receptor in the heart and its modulation using DHEA, was cardioprotective. Moreover, agonist-induced activation of the sigma-1 receptor modulates diverse ion channels and thereby regulates heart function. Novel concepts for understanding the pathophysiological relevance of sigma-1 receptors in the progression of heart failure, and developing clinical therapeutics targeting for the receptor in cardiovascular diseases are discussed.
  
  
  CONCLUSIONS
  Future studies should attempt to develop cardiac-specific knockdown of the sigma-1 receptor to observe its downstream signaling. We expect that these observations will lead to a novel therapeutic target for which a new class of antihypertrophic drugs can be designed.
authors.affiliation: Tohoku University, Graduate School of Pharmaceutical Sciences, Department of Pharmacology, Aramaki-Aoba Aoba-ku, Sendai 980-8578, Japan. fukunaga@mail.pharm.tohoku.ac.jp
authors.forename: Md Shenuarin
authors.initials: MS
authors.lastname: Bhuiyan
authors.forename: Kohji
authors.initials: K
authors.lastname: Fukunaga
mesh_terms: D000818:Animals; D001665:Binding Sites; D002316:Cardiotonic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000378:metabolism; D002319:Cardiovascular System / Q000503:physiopathology*; D002462:Cell Membrane / Q000378:metabolism; D003687:Dehydroepiandrosterone / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D008024:Ligands; D058990:Molecular Targeted Therapy; D032383:Myocytes, Cardiac / Q000502:physiology*; D051381:Rats; D017480:Receptors, sigma / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000097605:Sigma-1 Receptor
chemical_list: D002316:Cardiotonic Agents; D003687:Dehydroepiandrosterone; D008024:Ligands; D017480:Receptors, sigma; D000097605:Sigma-1 Receptor