{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,28]],"date-time":"2026-01-28T05:41:21Z","timestamp":1769578881410,"version":"3.49.0"},"reference-count":34,"publisher":"American Physiological Society","issue":"8","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2013,10,15]]},"abstract":"<jats:p>Although pentazocine binds to \u03c3<jats:sub>1<\/jats:sub>-receptor (\u03c3<jats:sub>1<\/jats:sub>R) with high affinity, the physiological relevance of its binding remains unclear. We first confirmed that \u03c3<jats:sub>1<\/jats:sub>R stimulation with pentazocine rescues contractile dysfunction following pressure overload (PO)-induced cardiac hypertrophy ovariectomized (OVX) female rats. In in vivo studies, vehicle, pentazocine (0.5\u20131.0 mg\/kg ip), and NE-100 (1.0 mg\/kg po), a \u03c3<jats:sub>1<\/jats:sub>R antagonist, were administered for 4 wk (once daily) starting from the onset of aortic banding after OVX. We also examined antihypertrophic effects of pentazocine (0.5\u20131 \u03bcM) in cultured cardiomyocytes exposed to angiotensin II. Pentazocine administration significantly inhibited PO-induced cardiac hypertrophy and rescued hypertrophy-induced impairment of cardiac dysfunctions such as left ventricular end-diastolic pressure, left ventricular developed pressure, and left ventricular contraction and relaxation (\u00b1dp\/dt) rates. Coadministration of NE-100 with pentazocine eliminated pentazocine-induced amelioration of heart dysfunction. Interestingly, pentazocine administration inhibited PO-induced \u03c3<jats:sub>1<\/jats:sub>R reduction and inositol-1,4,5-trisphosphate (IP<jats:sub>3<\/jats:sub>) receptor type 2 (IP<jats:sub>3<\/jats:sub>R2) upregulation in heart. Therefore, the reduced mitochondrial ATP production following PO was restored by pentazocine administration. Furthermore, we found that \u03c3<jats:sub>1<\/jats:sub>R binds to the ryanodine receptor (RyR) in addition to IP<jats:sub>3<\/jats:sub>receptor (IP<jats:sub>3<\/jats:sub>R) in cardiomyocytes. The \u03c3<jats:sub>1<\/jats:sub>R\/RyR complexes were decreased following OVX-PO and restored by pentazocine administration. We noticed that pentazocine inhibits the ryanodine-induced Ca<jats:sup>2+<\/jats:sup>release from sarcoplasmic reticulum (SR) in cultured cardiomyocytes. Taken together, the stimulation of \u03c3<jats:sub>1<\/jats:sub>R by pentazocine rescues cardiac dysfunction by restoring IP<jats:sub>3<\/jats:sub>R-mediated mitochondrial ATP production and by suppressing RyR-mediated Ca<jats:sup>2+<\/jats:sup>leak from SR in cardiomyocytes.<\/jats:p>","DOI":"10.1152\/ajpheart.00300.2013","type":"journal-article","created":{"date-parts":[[2013,8,10]],"date-time":"2013-08-10T04:42:22Z","timestamp":1376109742000},"page":"H1201-H1212","source":"Crossref","is-referenced-by-count":36,"title":["Diverse regulation of IP<sub>3<\/sub>and ryanodine receptors by pentazocine through \u03c3<sub>1<\/sub>-receptor in cardiomyocytes"],"prefix":"10.1152","volume":"305","author":[{"given":"Hideaki","family":"Tagashira","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan;"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Md. 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