Cardioprotection with kappa-opioid receptor stimulation is associated with a slowing of cross-bridge cycling.
Opioid and alpha-adrenergic receptor activation protect the heart from ischemic damage. One possible intracellular mechanism to explain this is that an improvement in ATP availability contributes to cardioprotection. We tested this hypothesis by correlating postischemic left ventricular developed pressure (LVDP) and myofibrillar Ca(2+)-dependent actomyosin Mg(2+)-ATPase from isolated rat hearts treated with the kappa-opioid receptor agonist U-50488H (1 microM) or the alpha-adrenergic receptor agonist phenylephrine (10 microM) + propranolol (3 microM). Preischemic treatment with U-50488H or phenylephrine + propranolol improved postischemic LVDP recovery by 25-30% over control hearts. Ca(2+)-dependent actomyosin Mg(2+)-ATPase was found to be 20% lower in both U-50488H- and phenylephrine + propranolol-treated hearts compared with control hearts. The kappa-opioid receptor antagonist nor-binaltorphimine (1 microM) abolished the effects of U-50488H on postischemic LVDP and actomyosin Mg(2+)-ATPase activity. Reduced actomyosin ATP utilization was also suggested in single ventricular myocytes treated with either U-50488H or the protein kinase C activator, phorbol 12-myristate 13-acetate (PMA), because U-50488H and PMA lowered maximum velocity of unloaded shortening by 15-25% in myocytes. U-50488H and phenylephrine + propranolol treatment both resulted in increased phosphorylation of troponin I and C protein. These findings are consistent with the hypothesis that kappa-opioid and alpha-adrenergic receptors decrease actin-myosin cycling rate, leading to a conservation of ATP and cardioprotection during ischemia.
Pyle
W G
WG
Department of Physiology, University of Tennessee, Memphis, Tennessee 38163, USA.
Smith
T D
TD
Hofmann
P A
PA
D000818:Animals; D005260:Female; D006321:Heart / Q000502:physiology*; D066298:In Vitro Techniques; D009124:Muscle Proteins / Q000378:metabolism; D009200:Myocardial Contraction / Q000502:physiology; D009206:Myocardium / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism; D009218:Myosins / Q000378:metabolism*; D010766:Phosphorylation; D011312:Pressure; D051381:Rats; D017208:Rats, Wistar; D017473:Receptors, Opioid, kappa / Q000502:physiology*; D013997:Time Factors; D016277:Ventricular Function, Left
D009124:Muscle Proteins; D017473:Receptors, Opioid, kappa; D009218:Myosins