Inhibition of [<sup>3</sup>H]‐U69593 binding and the cardiac effects of U50,488H by calcium channel blockers in the rat heart

Zhang, Weimin; Wang, Hongxin; Xia, Qiang; Wong, Tak‐Ming

doi:10.1038/sj.bjp.0700985

Cited by 11 publications

(4 citation statements)

References 45 publications

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“…Nor‐BNI was purchased from Tocris Cookson Ltd. (UK). The dose range of U50,488H used in the present study was 2.5–40 μM as the agonist at this dose range increased [Ca 2+ ] i and IP 3 , as well as suppressing cyclic AMP, and the effects were antagonized by nor‐BNI at the range of 1–5 μM (Sheng et al , 1997; Zhang et al , 1997; Zhang & Wong, 1998), which itself had no effect on any of the preparation studied. The concentrations of the PKC agonist and antagonists used were based on previous studies [PMA (Capogrossi et al , 1990; Schluter, 1995), staurosporine (Ventura et al , 1991) and chelerythrine (Kandasamy et al , 1995)].…”

Section: Methodsmentioning

confidence: 69%

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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Section: Methodsmentioning

confidence: 69%

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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“…i transient was determined by a spectrof luorometric method described previously [18,19]. Isolated ventricular myocytes were incubated with fura-2/AM at a concentration of 4 µM in a Joklik solution supplemented with 1.25 mM CaCl 2 for 25 min.…”

Section: Methodsmentioning

confidence: 99%

Antiarrhythmic Effect of Acupuncture Pretreatment in Rats Subjected to Simulative Global Ischemia and Reperfusion — Involvement of Adenylate Cyclase, Protein Kinase A, and L-Type Ca2+ Channel

et al. 2008

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Our previous study showed that electro-acupuncture (EA) pretreatment protects the heart from injury of ischemia. The present study explored further whether adenylate cyclase (AC), protein kinase A (PKA), and L-type Ca 2+ channel, the β 1 -AR signaling components modulating intracellular Ca 2+ ([Ca 2+ ] i ), are involved in the mediation of the antiarrhythmic effect of EA pretreatment in the rats from which the hearts were subsequently isolated and subjected to simulative global ischemia and reperfusion (SGIR). SGIR was performed by perfusing the isolated heart at a low flow followed by normal perfusion. Adult rats were randomized into four groups, namely, normal control (NC), SGIR, EA, and NC plus EA (NCEA) groups. The rats in the EA and NCEA groups were given EA pretreatment at bilateral Neiguan points (PC6) for 30 min once a day in 3 consecutive days before the hearts were isolated and perfused. The arrhythmia score and the response of [Ca 2+ ] i to the activators of AC, PKA, and L-type Ca 2+ channel in single ventricular myocyte isolated from the hearts subjected to SGIR were compared among the groups. The results showed that the arrhythmia score was significantly higher in the SGIR group as compared with the NC and NCEA groups. The SGIR-enhanced arrhythmia score was significantly attenuated in the EA group. More interesting, EA pretreatment also attenuated the SGIRenhanced response of [Ca 2+ ] i to the activators of AC, PKA, and the L-type Ca 2+ channel in the myocytes isolated from the hearts subjected to SGIR. In conclusion, EA pretreatment can produce an antiarrhythmic effect in the rat of SGIR. AC, PKA and the L-type Ca 2+ channel are involved in the mediation of the antiarrhythmic effect of EA pretreatment.

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“…In experiments conducted during extracellular acidosis the -opioid agonist was administered for 10 min after the perfusion of a solution at pH e 6.8 for 10 min because we also found that the effect of acidosis reached the maximum at ϳ10 min. The dose range used in the present study has been shown to increase the [Ca 2ϩ ] i and inositol 1,4,5-trisphosphate level, effects antagonized by 1-5 mM nor-BNI (51,54,55), which itself had no effect on any of the preparations studied. In a preliminary experiment, 10 µM EIPA did not alter the autofluorescence of the cell at the BCECF excitation wavelength as previously reported (29).…”

Section: Methodsmentioning

confidence: 59%

“…Both -opioid receptors (27,44,45,53,54) and -opioid peptides (48) are present in the heart. Previous studies have shown that during myocardial ischemia the -opioid receptor is activated presumably because of an increased release of -opioid peptides from the heart (50,51).…”

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confidence: 99%

Acidosis antagonizes intracellular calcium response to κ-opioid receptor stimulation in the rat heart

Pei

Bian

et al. 1999

American Journal of Physiology-Cell Physiology

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To study the effects of κ-opioid receptor stimulation on intracellular Ca2+ concentration ([Ca2+]i) homeostasis during extracellular acidosis, we determined the effects of κ-opioid receptor stimulation on [Ca2+]iresponses during extracellular acidosis in isolated single rat ventricular myocytes, by a spectrofluorometric method. U-50488H (10–30 μM), a selective κ-opioid receptor agonist, dose dependently decreased the electrically induced [Ca2+]itransient, which results from the influx of Ca2+ and the subsequent mobilization of Ca2+ from the sarcoplasmic reticulum (SR). U-50488H (30 μM) also increased the resting [Ca2+]iand inhibited the [Ca2+]itransient induced by caffeine, which mobilizes Ca2+ from the SR, indicating that the effects of the κ-opioid receptor agonist involved mobilization of Ca2+ from its intracellular pool into the cytoplasm. The Ca2+responses to 30 μM U-50488H were abolished by 5 μM nor-binaltorphimine, a selective κ-opioid receptor antagonist, indicating that the event was mediated by the κ-opioid receptor. The effects of the agonist on [Ca2+]iand the electrically induced [Ca2+]itransient were significantly attenuated when the extracellular pH (pHe) was lowered to 6.8, which itself reduced intracellular pH (pHi) and increased [Ca2+]i. The inhibitory effects of U-50488H were restored during extracellular acidosis in the presence of 10 μM ethylisopropyl amiloride, a potent Na+/H+exchange blocker, or 0.2 mM Ni2+, a putative Na+/Ca2+exchange blocker. The observations indicate that acidosis may antagonize the effects of κ-opioid receptor stimulation via Na+/H+and Na+/Ca2+exchanges. When glucose at 50 mM, known to activate the Na+/H+exchange, was added, both the resting [Ca2+]iand pHi increased. Interestingly, the effects of U-50488H on [Ca2+]iand the electrically induced [Ca2+]itransient during superfusion with glucose were significantly attenuated; this mimicked the responses during extracellular acidosis. When a high-Ca2+ (3 mM) solution was superfused, the resting [Ca2+]iincreased; the increase was abolished by 0.2 mM Ni2+, but the pHi remained unchanged. Like the responses to superfusion with high-concentration glucose and extracellular acidosis, the responses of the [Ca2+]iand electrically induced [Ca2+]itransients to 30 μM U-50488H were also significantly attenuated. Results from the present study demonstrated for the first time that extracellular acidosis antagonizes the effects of κ-opioid receptor stimulation on the mobilization of Ca2+ from SR. Activation of both Na+/H+and Na+/Ca2+exchanges, leading to an elevation of [Ca2+]i, may be responsible for the antagonistic action of extracellular acidosis against κ-opioid receptor stimulation.

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Inhibition of [³H]‐U69593 binding and the cardiac effects of U50,488H by calcium channel blockers in the rat heart

Cited by 11 publications

References 45 publications

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

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

Antiarrhythmic Effect of Acupuncture Pretreatment in Rats Subjected to Simulative Global Ischemia and Reperfusion — Involvement of Adenylate Cyclase, Protein Kinase A, and L-Type Ca2+ Channel

Acidosis antagonizes intracellular calcium response to κ-opioid receptor stimulation in the rat heart

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Inhibition of [3H]‐U69593 binding and the cardiac effects of U50,488H by calcium channel blockers in the rat heart

Cited by 11 publications

References 45 publications

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

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

Antiarrhythmic Effect of Acupuncture Pretreatment in Rats Subjected to Simulative Global Ischemia and Reperfusion — Involvement of Adenylate Cyclase, Protein Kinase A, and L-Type Ca2+ Channel

Acidosis antagonizes intracellular calcium response to κ-opioid receptor stimulation in the rat heart

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Inhibition of [³H]‐U69593 binding and the cardiac effects of U50,488H by calcium channel blockers in the rat heart