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

S. Fujita, S. C. Smart and D. F. Stowe. Enhanced Contractile Responsiveness to Cytosolic Ca2+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 opioidδ2 [D-Ala2]-deltorphin (DTP) and μ peptide agonist [D-Ala2]-enkephalin (DAMGO) alter the left ventricular pressure (LVP) [Ca2+]irelationship in isolated guinea pig hearts. LV phasic [Ca2+]iwas measured from dual fluorescence signals using indo 1. Ca2+transients were corrected and calibrated to n [Ca2+]i. Diastolic (d), systolic (s) [Ca2+]i, and s–d[Ca2+]iwere plotted v LVP at 0.3 to 6.8 m [CaCl2]eto assess the association of contractility to Ca2+. Also given were naltriben (NTB) and CTOP, δ2and μ antagonists, and nifedipine (NIF) and thapsigargin (THAP). From a control of 880±95 n (SEM), DTP decreased s–d[Ca2+]maxto 525±82 n after DTP and to 405±84 n after NIF, whereas THAP increased s–d[Ca2+]maxto 1605±275 n . NTB, 795±33 n , NTB+DTP, 820±98 n , DAMGO, 970±82 n , and DAMGO+CTOP, 830±93 n , gave values similar to controls. From a control value of 61±4 mmHg, LVPmaxwas 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 , less s–d[Ca2+]iwas required to attain 50% s–dLVPmax(curve left shift) with increasing [CaCl2]efor DTP, 407±17 n , and more was required for THAP, 737±35 n . DTP raised the slope max of s–dLVPmax(100%) v s–d[Ca2+]iby 2.7-fold. This indicates DTP enhances cardiac performance by enhancing responsiveness to cytosolic Ca2+rather than by raising diastolic Ca2+and subsequently released Ca2+, as does THAP.