TY - JOUR
T1 - Targeting sigma-1 receptor signaling by endogenous ligands for cardioprotection
AU - Bhuiyan, Md Shenuarin
AU - Fukunaga, Kohji
N1 - Funding Information:
This work was supported in part by grants-in-aid for Scientific Research 19390150 (to K Fukunaga) from the Ministry of Education, Science, Sports and Culture of Japan.
PY - 2011/2
Y1 - 2011/2
N2 - Introduction: 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. Areas covered: 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. Expert opinion: 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.
AB - Introduction: 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. Areas covered: 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. Expert opinion: 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.
KW - Akt
KW - cardiac hypertrophy
KW - cardiovascular diseases
KW - dehydroepiandrosterone
KW - sigma-1 receptor
UR - http://www.scopus.com/inward/record.url?scp=78651373483&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=78651373483&partnerID=8YFLogxK
U2 - 10.1517/14728222.2011.546350
DO - 10.1517/14728222.2011.546350
M3 - Review article
C2 - 21204730
AN - SCOPUS:78651373483
VL - 15
SP - 145
EP - 155
JO - Expert Opinion on Therapeutic Targets
JF - Expert Opinion on Therapeutic Targets
SN - 1472-8222
IS - 2
ER -