Signal Transduction in the Cardiac k-Receptor

Wong, TM; Sheng, Jian‐Zhong; Wong, Nai Sum; Tai, KK

doi:10.1159/000109438

Cited by 5 publications

(3 citation statements)

References 16 publications

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“…It was shown that stimulation of κ opioid receptors in myocytes was coupled with PLC activation via PTX-sensitive G proteins [4,42]. Accordingly, the inactivation of PTX-sensitive G proteins abolished the effects of κ opioid receptor stimulation on the [Ca 2+ ] i transient in the rat ventricular myocyte [30].…”

Section: Discussionmentioning

confidence: 99%

Opioid receptor-mediated effects of interleukin-2 on the [Ca2+]i transient and contraction in isolated ventricular myocytes of the rat

Cao

Xia

Chen

et al. 2001

Pflügers Arch - Eur J Physiol

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Cytokines play significant roles in some cardiovascular disorders, but direct myocardial effects of cytokines remain to be elucidated. In this study, we examined the effects and possible mechanisms of interleukin-2 (IL-2) on contraction and the [Ca2+]i transient of enzymatically isolated ventricular myocytes with spectrofluorometry and video tracking. IL-2 (2.5-200 U/ml) depressed both the contraction and the [Ca2+]i transient in a dose-dependent manner. Pretreatment with the universal opioid receptor antagonist naloxone (10 nM), or a specific kappa opioid receptor antagonist, nor-binaltorphimine (nor-BNI, 10 nM), abolished the inhibitory effect of IL-2 on contraction and the [Ca2+]i transient; the specific delta-opioid receptor antagonist naltrindole (1 microM) had no effect. The effect of IL-2 was also abolished after pretreatment with pertussis toxin (PTX, 5 mg/l), but not by genistein (100 microM). Pretreatment with the phospholipase C inhibitor U73122 (5 microM) significantly inhibited the IL-2-induced depression of contraction and the [Ca2+]i transient. It is concluded that the effects of IL-2 on contraction and the [Ca2+]i transient of ventricular myocytes are mediated via the cardiac kappa opioid receptor, and the postreceptor signal transduction pathway includes a PTX-sensitive G protein and phospholipase C.

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Section: Discussionmentioning

confidence: 99%

Opioid receptor-mediated effects of interleukin-2 on the [Ca2+]i transient and contraction in isolated ventricular myocytes of the rat

Cao

Xia

Chen

et al. 2001

Pflügers Arch - Eur J Physiol

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“…Kappa receptors are found throughout the heart, but are most prominent in the right atrium and are functionally altered in response to hemorrhagic shock in the right atrium and ventricle (Krumins et al, 1985). Activation of kappa receptors in ventricular myocytes leads to a release of intracellular calcium (Wong et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

Effects of kappa opioid agonists alone and in combination with cocaine on heart rate and blood pressure in conscious squirrel monkeys

Schindler¹,

Graczyk²,

Gilman³

et al. 2007

European Journal of Pharmacology

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As kappa agonists have been proposed as treatments for cocaine abuse, the cardiovascular effects of the kappa opioid receptor agonists ethylketocyclazocine (EKC) and enadoline were investigated in conscious squirrel monkeys. Both EKC and enadoline increased heart rate with little effect on blood pressure. This effect appeared to be specific for kappa receptors as the mu opioid agonist morphine did not mimic the effects of the kappa agonists. The opioid antagonist naltrexone, at a dose of 1.0 mg/kg, blocked the effect of EKC. An action at both central and peripheral receptors may be responsible for the heart rate increase following kappa agonist treatment. The ganglionic blocker chlorisondamine partially antagonized the effect of EKC on heart rate, suggesting central involvement, while the peripherally-acting agonist ICI 204,448 ((±)-1-[2,3-(Dihydro-7-methyl-1H-inden-4-yl)oxy]-3-[(1-methylethyl)amino]-2-butanol hydrochloride) also increased heart rate, supporting a peripheral site of action. When given in combination with cocaine, EKC produced effects that were sub-additive, suggesting that the kappa agonists may be used safely as cocaine abuse treatments.

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“…Previous studies have shown that cardiac K ‐receptor stimulation results in a reduction in contractility of the heart and arrhythmias, both of which are believed to be due to alterations in Ca 2+ homeostasis in the heart (Ventura et al , 1992; Wong et al , 1995). The alterations in Ca 2+ homeostasis have been shown to result from suppression of the AC/cyclic AMP pathway and activation of the PLC‐IP 3 /Ca 2+ pathway (Ventura et al , 1992; Sheng et al , 1997; Zhang & Wong, 1998).…”

Section: Discussionmentioning

confidence: 99%

Effects of κ‐opioid receptor stimulation in the heart and the involvement of protein kinase C

Bian¹,

Wang²,

Zhang³

et al. 1998

British J Pharmacology

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1 The role of protein kinase C (PKC) in mediating the action of k-receptor stimulation on intracellular Ca 2+ and cyclic AMP production was determined by studying the e ects of trans-(+)-3,4-dichloro-Nmethyl-N-(2-[1-pyrrolidinyl] cyclohexyl) benzeneacetamide methanesulphonate (U50,488H), a selective k-receptor agonist, and phorbol 12-myristate 13-acetate (PMA), a PKC agonist, on the electricallyinduced [Ca 2+ ] i transient and forskolin-stimulated cyclic AMP accumulation in the presence and absence of a PKC antagonist, staurosporine or chelerythrine, in the single rat ventricular myocyte. 2 U50,488H at 2.5 ± 40 mM decreased both the electrically-induced [Ca 2+ ] i transient and forskolinstimulated cyclic AMP accumulation dose-dependently, e ects which PMA mimicked. The e ects of the k-agonist, that were blocked by a selective k-antagonist, nor-binaltorphimine, were signi®cantly antagonized by the PKC antagonists, staurosporine and/or chelerythrine. The results indicate that PKC mediates the actions of k-receptor stimulation. 3 To determine whether the action of PKC was at the sarcoplasmic reticulum (SR) or not, the [Ca 2+ ] i transient induced by ca eine, that depletes the SR of Ca 2+ , was used as an indicator of Ca 2+ content in the SR. The ca eine-induced [Ca 2+ ] i transient was signi®cantly reduced by U50,488H at 20 mM. This e ect of U50,488H on ca eine-induced [Ca 2+ ] i transient was signi®cantly attenuated by 1 mM chelerythrine, indicating that the action of PKC involves mobilization of Ca 2+ from the SR. When the increase in IP 3 production in response to k-receptor stimulation with U50,488H in the ventricular myocyte was determined, the e ect of U50,488H was the same in the presence and absence of staurosporine, suggesting that the e ect of PKC activation subsequent to k-receptor stimulation does not involve IP 3 . The observations suggest that PKC may act directly at the SR. 4 In conclusion, the present study has provided evidence for the ®rst time that PKC may be involved in the action of k-receptor stimulation on Ca 2+ in the SR and cyclic AMP production, both of which play an essential role in Ca 2+ homeostasis in the heart.

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Signal Transduction in the Cardiac k-Receptor

Cited by 5 publications

References 16 publications

Opioid receptor-mediated effects of interleukin-2 on the [Ca2+]i transient and contraction in isolated ventricular myocytes of the rat

Opioid receptor-mediated effects of interleukin-2 on the [Ca2+]i transient and contraction in isolated ventricular myocytes of the rat

Effects of kappa opioid agonists alone and in combination with cocaine on heart rate and blood pressure in conscious squirrel monkeys

Effects of κ‐opioid receptor stimulation in the heart and the involvement of protein kinase C

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