Enhanced contractile responsiveness to cytosolic Ca2+ by delta-2 opioid agonist deltorphin in intact guinea pig hearts

Opioid receptor subtypes delta and kappa, are found in cardiac tissue and m ay play a role in cardiac function. We explored if the synthetic opioid del ta(2) [D-Ala(2)]-deltorphin (DTP) and mu peptide agonist [D-Ala(2)]-enkepha lin (DAMGO) alter the left ventricular pressure (LVP) [Ca2+](i) relationshi p in isolated guinea pig hearts. LV phasic [Ca2+](i) was measured from dual fluorescence signals using indo 1. Ca2+ transients were corrected and cali brated to nM [Ca2+](i). Diastolic (d), systolic (s) [Ca2+](i), and s-d[Ca2](i) were plotted v LVP at 0.3 to 6.8 mM [CaCl2](e) to assess the associati on of contractility to Ca2+. Also given were naltriben (NTB) and CTOP, delt a(2) and mu antagonists, and nifedipine (NIF) and thapsigargin (THAP). From a control of 880 +/- 95 nM (SEM), DTP decreased s-d[Ca2+](max) to 525 +/- 82 nM after DTP and to 405 +/- 84 nM after NIF, whereas THAP increased s-d[ Ca2+](max) to 1605 +/- 275 nM. NTB, 795 +/- 33 nM, NTB + DTP, 820 +/- 98 nM , DAMGO, 970 +/- 82 nM, and DAMGO + CTOP, 830 +/- 93 nM, gave values simila r to controls, From a control value of 61 +/- 4 mmHg, LVPmax was increased by DTP to 73 +/- 3 mmHg and by THAP to 77 +/- 2 mmHg, was unchanged by DAMG O at 48 +/- 6 mmHg, and was decreased by NIF to 24 +/- 2 mmHg. Compared to the control value of 594 +/- 18 nM, less s-d[Ca2+](i) was required to attai n 50% s-dLVP(max) (curve left shift) with increasing [CaCl2](e) for DTP, 40 7 +/- 17 nM. and more was required for THAP, 737 +/- 35 nM. DTP raised the slope max of s-dLVP(max) (100%) v s-d[Ca2+](i) by 2.7-fold, This indicates DTP enhances cardiac performance by enhancing responsiveness to cytosolic C a2+ rather than by raising diastolic Ca2+ and subsequently released Ca2+, a s does THAP. (C) 2000 Academic Press.