Enhanced contractile responsiveness to cytosolic Ca(2+) by delta-2 opioid agonist deltorphin in intact guinea pig hearts.
Opioid receptor subtypes, delta and kappa, are found in cardiac tissue and may play a role in cardiac function. We explored if the synthetic opioid delta(2)[D-Ala(2)]-deltorphin (DTP) and mu 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 nM [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 mM [CaCl(2)](e)to assess the association of contractility to Ca(2+). Also given were naltriben (NTB) and CTOP, delta(2) and mu antagonists, and nifedipine (NIF) and thapsigargin (THAP). From a control of 880+/-95 nM (SEM), DTP decreased s-d[Ca(2+)](max) to 525+/-82 nM after DTP and to 405+/-84 nM after NIF, whereas THAP increased s-d[Ca(2+)](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 similar to controls. From a control value of 61+/-4 mm Hg, 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 nM, 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 nM, and more was required for THAP, 737+/-35 nM. 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.
Fujita
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Department of Anesthesiology, Anesthesiology Research Laboratories, Milwaukee, WI 53226, USA.
Smart
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SC
Stowe
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D000818:Animals; D002118:Calcium / Q000502:physiology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000494:pharmacology; D006168:Guinea Pigs; D006321:Heart / Q000502:physiology*; D009200:Myocardial Contraction / Q000187:drug effects* / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology*; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000502:physiology*; D015398:Signal Transduction
D009842:Oligopeptides; D017465:Receptors, Opioid, delta; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; C059567:deltorphin; D002118:Calcium