kappa-Opioid receptor stimulation inhibits augmentation of Ca(2+) transient and hypertrophy induced by isoprenaline in neonatal rat ventricular myocytes - Role of CaMKIIdelta(B).
We aimed to further define the pathway mediating the inhibitory effects of kappa-opioid receptor stimulation on Ca(2+) transients and hypertrophic responses to beta(1)-adrenoceptor stimulation. We determined the effects of trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamid methanesulfonate salt (U50,488H), a selective kappa-opioid receptor agonist, on the enhancement of spontaneous Ca(2+) transients and the induction of hypertrophy by isoprenaline, a beta-adrenoceptor agonist, in cultured neonatal ventricular myocytes. The results were compared with those found with KN93, a selective Ca(2+)/calmodulin-dependent kinase (CaMKII) inhibitor, propranolol, a beta-adrenoceptor antagonist, and verapamil, a L-type Ca(2+) channel antagonist. Hypertrophy of cardiomyocytes was characterized by increases in (i) total protein content; (ii) cell size; and (iii) [(3)H]leucine incorporation. 10 micromol/l isoprenaline increased all three parameters. We also determined the expression of nuclear CaMKIIdelta in response to U50,488H in the presence or absence of isoprenaline. To determine whether the effects of U50,488H were receptor-mediated, its effects were also measured following blockade of the kappa-opioid receptor with nor-binaltorphimine. kappa-Opioid receptor stimulation suppressed the stimulatory effect of isoprenaline on Ca(2+) transients and cardiac hypertrophy, as did KN93, propranalol and verapamil. U50,488H also suppressed the expression of nuclear CaMKIIdelta(B) in the presence, but not in the absence of isoprenaline. These results suggest that the inhibitory effect of kappa-opioid receptor stimulation on beta(1)-adrenoceptor stimulation may also involve CaMKIIdelta.
Wu
Guoqiang
G
Key Laboratory of Molecular Biology & Drug Research, Liaoning Medical College, Liaoning, PR China.
Wang
Hongxin
H
Yang
Jing
J
Yang
Yuhong
Y
Liu
Chunna
C
Jing
Li
L
Wong
Tak Ming
TM
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology*; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001596:Benzylamines / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020013:Calcium Signaling / Q000187:drug effects*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002467:Cell Nucleus / Q000187:drug effects / Q000201:enzymology; D048429:Cell Size / Q000187:drug effects*; D002478:Cells, Cultured; D006984:Hypertrophy; D007545:Isoproterenol / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects* / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D013449:Sulfonamides / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology; D000096926:Benzenesulfonamides
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D001596:Benzylamines; D002121:Calcium Channel Blockers; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D007545:Isoproterenol; D009271:Naltrexone; D009292:Narcotic Antagonists; D011433:Propranolol; D047428:Protein Kinase Inhibitors; D018342:Receptors, Adrenergic, beta-1; D017473:Receptors, Opioid, kappa; D013449:Sulfonamides; D014700:Verapamil; C072105:KN 93; D000096926:Benzenesulfonamides; C051844:norbinaltorphimine; C517677:Camk2d protein, rat