Opioid Peptide Deltorphin II Simulates the Cardioprotective Effect of Ischemic Preconditioning: Role of δ2-Opioid Receptors, Protein Kinase C, and KATP Channels

Maslov, L. N.; Barzakh, E. I.; Чернышева, Г. А.; Krieg, Thomas; Solenkova, Nataliya V.; Lishmanov, A. Yu.; Cybulnikov, S. Yu.; Zhang, Y.

doi:10.1007/s10517-010-1000-6

Cited by 10 publications

(10 citation statements)

References 12 publications

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“…Cell suspensions with more than 85% viability were plated and cultured for further experiments. The cells were grown uniformly and seeded in 25 cm 2 flasks at the density of 1x10 6 /l and then maintained in culture containing …”

Section: Methodsmentioning

confidence: 99%

“…Studies have found that the agonist of the δ-opioid receptor stimulates the proliferation of neonatal rat cardiac myocytes (5) and mimics the protective effects of ischemic preconditioning on heart and brain tissue (6,7). These findings have demonstrated that the δ-opioid receptor plays a significant role in the growth and maintenance of cells.…”

Section: Introductionmentioning

confidence: 99%

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Activation of the δ-opioid receptor inhibits serum deprivation-induced apoptosis of human liver cells via the activation of PKC and the mitochondrial pathway

Wang¹

2011

Int J Mol Med

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Abstract. Apoptosis of human liver cells is commonly found in liver diseases and liver surgery and directly affects their prognosis. Recent studies have found that δ-opioid receptors, abundant in the membranes of hepatic cells, participate in the oncogenesis and progression of liver tumors, viral hepatitis, liver cirrhosis and other diseases. The purpose of this study was to analyze the effect of the activation of the δ-opioid receptor on liver cell apoptosis and explore its relationship with PKC and the mitochondrial pathway. Hepatic cells were serum-deprived to induce apoptosis in vitro. During the period of apoptosis, mitochondrial membrane potential decreased, protein levels of cytosolic cytochrome c increased and the expression of Bcl-2 decreased, indicating that apoptosis was specifically induced by the mitochondrial pathway. Importantly, activation of δ-opioid receptors reversed the apoptotic state of hepatic cells. Following δ-opioid receptor activation, the mitochondrial membrane potential remained stable, and the expression of cytosolic cytochrome c and Bax decreased. These data suggest that δ-opioid receptor activation specifically inhibits the mitochondrial apoptotic pathway. In addition, activation of the δ-opioid receptor apparently increased the levels of PKC; blocking the PKC pathway led to increased apoptosis of liver cells, which was not affected by the activation of δ-opioid receptor. Blocking the PKC pathway led to increased apoptosis of liver cells, which was associated with δ-opioid receptor activation. Therefore, the PKC pathway is involved in the anti-apoptotic effects of the δ-opioid receptor on liver cells.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Activation of the δ-opioid receptor inhibits serum deprivation-induced apoptosis of human liver cells via the activation of PKC and the mitochondrial pathway

Wang¹

2011

Int J Mol Med

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“… ‡ [1] (van Rijn et al 2010), [2] (Saitoh et al 2005) [3], (Margolis et al 2008), [4] (Sugiyama et al 2012), [5] (Randall-Thompson et al 2010), [6] (Krishnan-Sarin et al 1995) [7] (van Rijn and Whistler 2009), [8] (Matsuzawa et al 1998), [9] (Bie et al 2009a), [10] (van Rijn et al 2012a), [11] (Kamei et al 1994b), [12] (Kamei et al 1993b), [13] (Kamei et al 1991), [14] (Tortella et al 1984), [15] (Tortella et al 1988), [16] (Saitoh et al 2011), [17] (Yajima et al 2000), [18] (Di Giannuario et al 2001), [19] (Capasso and Cavallo 2005), [20] (Mizoguchi et al 1996), [21] (Fraser et al 2000b), [22](Sharp et al 1998), [23] (Miyamoto et al 1994), [24] (Miyamoto et al 1993a), [25] (Miyamoto et al 1993b), [26] (Suzuki et al 1997), [27] (Broccardo and Improta 1992b), [28] (Broccardo and Improta 1992a), [29] (Krevsky et al 1991), [30] (Fox-Threlkeld et al 1994), [31] (Pairet and Ruckebusch 1984), [32] (Shook et al 1989), [33] (Torregrossa et al 2006), [34] (Charron et al 2008), [35] (Maslov et al 2010b), [36] (Maslov et al 2010a), [37] (Guo et al 2005), [38] (Yang et al 2011), [39] (Lasukova et al 2009), [40] (Stewart and Hammond 1994), [41] (Mika et al 2001), [42] (Taiwo and Levine 1991), [43] (Fraser et al 2000a), [44] (Hurley and Hammond 2000), [45] (Cahill et al 2003), [46] (Holdridge and Cahill 2007), [47] (Ukai et al 1997), [48] (Castellano and Pavone 1985) …”

Section: Figurementioning

confidence: 99%

“…However, it appears that DOR subtype selectivity plays less of an important role for some other potential DOR-mediated side effects. Many DOR1- and DOR2-subtype selective agonists (DPDPE (Charron et al 2008; Lasukova et al 2009; Yang et al 2011), SNC-121(Patel et al 2006), Eribis peptide 94(Karlsson et al 2011), fentanyl isothiocyanate[FIT] (Gross et al 2005), BW373U86 (Peart et al 2011), TAN-67 (Guo et al 2005), ARD-353 (Watson et al 2006), deltorphin II (Maslov et al 2010a) have cardioprotective abilities. While a study by Mslov et al suggested that only the DOR2 selective deltorphin II, but not DPDPE, reduced infarct size (Maslov et al 2010b), these differences may relate to experimental procedures (e.g.…”

Section: Introductionmentioning

confidence: 99%

Pharmacological traits of delta opioid receptors: pitfalls or opportunities?

2013

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Delta opioid receptors (DORs) have been considered as a potential target to relieve pain as well as treat depression and anxiety disorders, and are known to modulate other physiological responses, including ethanol and food consumption. A small number of DOR selective drugs are in clinical trials, but no DOR selective drugs have been approved by the Federal Drug Administration and some candidates have failed in phase II clinical trials, highlighting current difficulties producing effective delta opioid based therapies. Recent studies have provided new insights into the pharmacology of the DOR, which is often complex and at times paradoxical. This review will discuss the existing literature focusing on four aspects: 1) Two DOR subtypes have been postulated based on differences in pharmacological effects of existing DOR-selective ligands 2) DORs are expressed ubiquitously throughout the body and central nervous system and are, thus, positioned to play a role in a multitude of diseases. 3) DOR expression is often dynamic, with many reports of increased expression during exposure to chronic stimuli, such as stress, inflammation, neuropathy, morphine, or changes in endogenous opioid tone. 4) A large structural variety in DOR ligands implies potential different mechanisms of activating the receptor. These combined features of DOR pharmacology illustrate the potential benefit of designing tailored or biased DOR ligands.

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“…A number of studies have shown that δ receptor activation may promote the proliferation of rat myocardial cells (8,9) and imitate ischemia preconditioning to protect the heart and brain (10,11). As studies of δ receptor functions have continued, it has been shown that the δ receptor is critical in the regulation of the onset and development of cardiac diseases.…”

Section: Introductionmentioning

confidence: 99%

Alpinetin activates the δ receptor instead of the κ and μ receptor pathways to protect against rat myocardial cell apoptosis

Suo¹,

Sun

Yang³

2013

Experimental and Therapeutic Medicine

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Alpinetin is a natural flavonoid that protects cells against fatal injury in ischemia-reperfusion. δ receptor activation protects myocardial cells from trauma; however, the mechanism is unknown. The aim of this study was to explore the function of alpinetin in δ receptor-mediated myocardial apoptosis. The myocardial cells of newly born rats were cultivated and myocardial apoptosis was induced by serum deprivation. The MTT method was used to evaluate cell viability and Annexin V-fluorescein isothiocyanate (FITC)/propidium iodide (PI) staining was used to analyze apoptosis. The expression levels of opioid receptor mRNA and protein were tested using reverse transcription-polymerase reaction (RT-PCR) and western blot assays. In addition, an opioid receptor antagonist, as well as protein kinase C (PKC) and extracellular signal-regulated kinase (ERK) inhibitors, were used to determine the inferred signaling pathway. The results showed that that alpinetin reduced the myocardial apoptosis induced by serum deprivation in a concentration-dependent manner. However, the protection conferred to the myocardial cells by alpinetin was blocked by the δ opioid receptor antagonist naltrindole, as well as by PKC and ERK inhibitors (GF109203X and U0126, respectively). In addition, it was shown that alpinetin was able to maintain the stability of the mitochondrial membrane potential, lower the level of intracytoplasmic cytochrome c and reduce Bax displacement from the cytoplasm to the mitochondria. It was concluded that alpinetin was able to activate δ receptors to induce the endogenous protection of myocardial cells via the PKC/ERK signaling pathway.

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Opioid Peptide Deltorphin II Simulates the Cardioprotective Effect of Ischemic Preconditioning: Role of δ2-Opioid Receptors, Protein Kinase C, and KATP Channels

Cited by 10 publications

References 12 publications

Activation of the δ-opioid receptor inhibits serum deprivation-induced apoptosis of human liver cells via the activation of PKC and the mitochondrial pathway

Activation of the δ-opioid receptor inhibits serum deprivation-induced apoptosis of human liver cells via the activation of PKC and the mitochondrial pathway

Pharmacological traits of delta opioid receptors: pitfalls or opportunities?

Alpinetin activates the δ receptor instead of the κ and μ receptor pathways to protect against rat myocardial cell apoptosis

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