Kappa-opioid receptor stimulation inhibits growth of neonatal rat ventricular myocytes.
The effects of trans-(+/-)-3,4-dichloro-N-methyl-N-[2-(1-pyrrolidinyl)-cyclohexyl]-benzeneacetamide methanesulfonate salt (U50,488H), a selective kappa-opioid receptor agonist, on growth in neonatal ventricular myocytes were determined. In 15% serum culture medium, U50,488H at 0.1-1 microM significantly reduced the protein content, [3H]leucine uptake and cell size of the myocytes. The effect of U50,488H on protein content was abolished in the presence of 1 microM nor-binaltorphimine (nor-BNI), a selective kappa-opioid receptor antagonist. In a 0.4% serum medium, U50,488H at 0.1-1 microM had no effect on myocyte growth. Interestingly, 1 microM U50,488H abolished the stimulatory effects of 1 microM norepinephrine on protein content, [3H]leucine uptake and cell size of the myocytes in the low serum medium. The effect of U50,488H was abolished by 1 microM nor-BNI. With the exception of cell size, the effects of norepinephrine were completely abolished by blockade of both alpha- and beta-adrenoceptors, but only partially blocked by blockade of either adrenoceptors. These results provide first evidence that kappa-opioid receptor stimulation inhibits growth of the neonatal ventricular myocyte as a result of direct action as well as by inhibiting sympathetic stimulation of the heart. The stimulatory effects of sympathetic activity on growth occurs via both alpha- and beta-adrenoceptors.
Wang
Guijun
G
Department of Pharmacology, Jinzhou Medical College, Jinzhou, China.
Wang
Hongxin
H
Yang
Yanling
Y
Wong
Tak Ming
TM
D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D002455:Cell Division / Q000187:drug effects / Q000502:physiology; D048429:Cell Size / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007930:Leucine / Q000493:pharmacokinetics; D032383:Myocytes, Cardiac / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000378:metabolism*; D014316:Tritium
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D018712:Analgesics, Non-Narcotic; D011506:Proteins; D017473:Receptors, Opioid, kappa; D014316:Tritium; D019900:3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer; D011433:Propranolol; D007930:Leucine; D009638:Norepinephrine; D011224:Prazosin