Enhanced Contractile Responsiveness to Cytosolic Ca2+by Delta-2 Opioid Agonist Deltorphin in Intact Guinea Pig Hearts

Abstract S. Fujita, S. C. Smart and D. F. Stowe. Enhanced Contractile Responsiveness to Cytosolic Ca 2+ by Delta-2 Opioid Agonist Deltorphin in Intact Guinea Pig Hearts. Journal of Molecular and Cellular Cardiology (2000) 32 , 1647–1659. Opioid receptor subtypes, δ and κ , are found in cardiac tissue and may play a role in cardiac function. We explored if the synthetic opioid δ 2 [D-Ala 2 ]-deltorphin (DTP) and μ peptide agonist [D-Ala 2 ]-enkephalin (DAMGO) alter the left ventricular pressure (LVP) [Ca 2+ ] i relationship in isolated guinea pig hearts. LV phasic [Ca 2+ ] i was measured from dual fluorescence signals using indo 1. Ca 2+ transients were corrected and calibrated to n m [Ca 2+ ] i . Diastolic (d), systolic (s) [Ca 2+ ] i , and s–d[Ca 2+ ] i were plotted v LVP at 0.3 to 6.8 m m [CaCl 2 ] e to assess the association of contractility to Ca 2+ . Also given were naltriben (NTB) and CTOP, δ 2 and μ antagonists, and nifedipine (NIF) and thapsigargin (THAP). From a control of 880±95 n m (SEM), DTP decreased s–d[Ca 2+ ] max to 525±82 n m after DTP and to 405±84 n m after NIF, whereas THAP increased s–d[Ca 2+ ] max to 1605±275 n m . NTB, 795±33 n m , NTB+DTP, 820±98 n m , DAMGO, 970±82 n m , and DAMGO+CTOP, 830±93 n m , gave values similar to controls. From a control value of 61±4 mmHg, LVP max was increased by DTP to 73±3 mmHg and by THAP to 77±2 mmHg, was unchanged by DAMGO at 48±6 mmHg, and was decreased by NIF to 24±2 mmHg. Compared to the control value of 594±18 n m , less s–d[Ca 2+ ] i was required to attain 50% s–dLVP max (curve left shift) with increasing [CaCl 2 ] e for DTP, 407±17 n m , and more was required for THAP, 737±35 n m . DTP raised the slope max of s–dLVP max (100%) v s–d[Ca 2+ ] i by 2.7-fold. This indicates DTP enhances cardiac performance by enhancing responsiveness to cytosolic Ca 2+ rather than by raising diastolic Ca 2+ and subsequently released Ca 2+ , as does THAP.