Modulation of myofilament Ca2+ densitivity by delta- and kappa-opioid agonists in intact guinea pig hearts.
We investigated whether delta- and kappa-opioid agonists alter myocardial function, intracellular Ca(2+) concentration ([Ca(2+)](i)), and myofilament Ca(2+) sensitivity in intact guinea pig beating hearts and whether these effects are mediated by an opioid receptor. Intact guinea pig hearts were perfused with modified Krebs Ringer solution containing delta- (TAN-67) and kappa- (ICI-199441) opioid agonists in the absence and presence of delta- (BNTX) and kappa- (nor-BNI) opioid antagonists, respectively, while functional variables and [Ca(2+)](i) were recorded. TAN-67 (1 microM) and ICI-199441 (1 microM) decreased heart rate (P < 0.05). TAN-67 (1 microM) and ICI-199441 (1 micro M) decreased available [Ca(2+)](i) without changing developed left ventricular pressure (LVP) (P < 0.05). TAN-67 (1 microM) and ICI-199441 (1 microM) also caused a leftward shift in the curve of developed LVP as a function of available [Ca(2+)](i) (P < 0.05). ICI-199441 (1 microM) produced a steeper slope in the relation curve compared with baseline (P < 0.05). BNTX (1 microM) and nor-BNI (1 microM) blocked the effects of TAN-67 and ICI-199441, respectively. delta- and kappa-opioid agonists enhance myofilament Ca(2+) sensitivity despite decreasing available [Ca(2+)](i) in intact isolated guinea pig hearts, and these effects are mediated by delta- and kappa-opioid receptor stimulation.


CONCLUSIONS
Our results indicate that delta- and kappa-opioid agonists enhance myofilament Ca(2+) sensitivity despite decreasing available intracellular Ca(2+) concentrations in intact isolated guinea pig beating hearts, and these effects are mediated by delta- and kappa-opioid receptor stimulation.
Nakae
Yuri
Y
*Department of Anesthesiology, Sapporo Medical University School of Medicine; and †Departments of Anesthesiology and Critical Care Medicine, Asahikawa Medical College, Japan.
Fujita
Satoshi
S
Namiki
Akiyoshi
A
D008841:Actin Cytoskeleton / Q000187:drug effects*; D000818:Animals; D001597:Benzylidene Compounds / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002118:Calcium / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007700:Kinetics; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D011759:Pyrrolidines / Q000494:pharmacology; D011804:Quinolines / Q000494:pharmacology; D017465:Receptors, Opioid, delta / Q000819:agonists* / Q000037:antagonists & inhibitors; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000037:antagonists & inhibitors; D013268:Stimulation, Chemical; D016277:Ventricular Function, Left / Q000187:drug effects
D001597:Benzylidene Compounds; D009292:Narcotic Antagonists; D011759:Pyrrolidines; D011804:Quinolines; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; C094142:TAN 67; C058468:ICI 199441; C077358:7-benzylidenenaltrexone; C051844:norbinaltorphimine; D009271:Naltrexone; D002118:Calcium