Title |
Cardioprotective Effect of the Selective Sigma-1 Receptor Agonist, SA4503
|
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Published in |
Yakugaku Zasshi = Journal of Pharmaceutical Society of Japan, January 2014
|
DOI | 10.1248/yakushi.13-00255-3 |
Pubmed ID | |
Authors |
Kohga Hirano, Hideaki Tagashira, Kohji Fukunaga |
Abstract |
We previously reported that the sigma-1 receptor is down-regulated in cardiomyocytes following heart failure in transverse aortic constriction (TAC) mice. In this review, we summarized the anti-hypertrophic action of selective sigma-1 receptor agonist, SA4503 in the hypertrophied cultured cardiomyocytes and discussed its possible mechanism of cardioprotection. Treatment with SA4503 (0.1-1 μM) dose-dependently inhibited hypertrophy in cultured cardiomyocytes induced by angiotensin II (Ang II). We also found that α1 receptor stimulation by phenylephrine (PE) promotes ATP production through IP3 receptor-mediated Ca(2+) mobilization into mitochondria in cultured cardiomyocytes. Interestingly, the PE-induced ATP production was impaired after Ang II-induced hypertrophy and SA4503 treatment largely restored PE-induced ATP production. The impaired PE-induced ATP production was associated with reduced mitochondrial size. The SA4503 treatment completely restored mitochondrial size concomitant with restored ATP production. These effects were blocked by sigma-1 receptor antagonist, NE-100 and sigma-1 receptor siRNA. We also confirmed that chronic SA4503 administration also significantly attenuates myocardial hypertrophy and restores ATP production in transverse aortic constriction mice. Taken together, sigma-1 receptor stimulation with selective agonist SA4503 ameliorates cardiac hypertrophy and dysfunction by restoring both mitochondrial Ca(2+) mobilization and ATP production via sigma-1 receptor stimulation. Sigma-1 receptor stimulation represents a new therapeutic strategy to rescue heart from hypertrophic dysfunction in heart failure. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 13 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 2 | 15% |
Researcher | 2 | 15% |
Student > Master | 2 | 15% |
Student > Doctoral Student | 1 | 8% |
Other | 1 | 8% |
Other | 0 | 0% |
Unknown | 5 | 38% |
Readers by discipline | Count | As % |
---|---|---|
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 15% |
Chemistry | 2 | 15% |
Energy | 1 | 8% |
Neuroscience | 1 | 8% |
Medicine and Dentistry | 1 | 8% |
Other | 0 | 0% |
Unknown | 6 | 46% |