scholarly journals Characteristic MicroRNA Expression Induced by δ-Opioid Receptor Activation in the Rat Liver Under Prolonged Hypoxia

2017 ◽  
Vol 44 (6) ◽  
pp. 2296-2309 ◽  
Author(s):  
Feng Zhi ◽  
Naiyuan Shao ◽  
Lian Xue ◽  
Yuan Xu ◽  
Xuezhi Kang ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Mirna Expression ◽  
Ischemic Injury ◽  
Clinical Problem ◽  
Receptor Activation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Δ Opioid Receptor ◽  
Induced Changes ◽  
Hypoxic Ischemic Injury

Background/Aims: Hypoxic/ischemic injury to the liver is a frequently encountered clinical problem with limited therapeutic options. Since microRNAs (miRNAs) are involved in hypoxic/ ischemic events, and δ-opioid receptor (DOR) is protective against hypoxic/ischemic injury, we asked if pharmacological activation of DOR can alter hypoxic events by regulating miRNA expression in the liver. As the first step, the present work aimed at testing the effect of DOR activation on hepatic miRNA expression in hypoxia. Methods: Male Sprague Dawley rats were exposed to hypoxia (9.5-10% O2) for 1, 5, or 10 days with or without DOR activation. The target miRNAs were selected according to TaqMan low-density array (TLDA) data and analyzed by quantitative real-time PCR. Results: We found that: 1) 1-day hypoxia caused the upregulation of 9 miRNAs (miR-7a-5p, miR-10a-5p, miR-25-3p, miR-26b-5p, miR-122-5p, miR-128a-3p, miR-135b-5p, miR-145-5p, and miR-181a-5p) and the downregulation of 2 miRNAs (miR-34a-5p and miR-182); 2) 5 and 10-days hypoxia altered the expression of 4 miRNAs (miR-34c-5p, miR-184, miR-107-3p and miR192-5p); 3) DOR activation shifted the expression of 8 miRNAs (miR-122-5p, miR-146a-5p, miR-30e-5p, miR-128a-3p, miR-182, miR-192-5p miR-107-3p and miR-184) in normoxic condition; and 4) DOR activation modified hypoxia-induced changes in 6 miRNAs (miR-142-5p, miR-145-5p, miR-146a-5p, miR-204-5p, miR-34a-5p and miR-192-5p). Conclusion: Hypoxia significantly modifies the miRNA profile in the liver, while DOR activation can modify the hypoxic modification. Therefore, it is potentially possible to alter hypoxic/ischemic pathophysiology in the liver through DOR pharmacotherapy.

scholarly journals δ-Opioid Receptor Activation and MicroRNA Expression in the Rat Heart Under Prolonged Hypoxia

2016 ◽  
Vol 39 (3) ◽  
pp. 1118-1128 ◽  
Author(s):  
Feng Zhi ◽  
Lian Xue ◽  
Naiyuan Shao ◽  
Danni Deng ◽  
Xuezhi Kang ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Ischemic Injury ◽  
Receptor Activation ◽  
Sprague Dawley ◽  
Hypoxic Conditions ◽  
Mirna Expression Profiles ◽  
Δ Opioid Receptor ◽  
Hypoxic Ischemic Injury

Background: Hypoxic/ischemic injury to the heart is a frequently encountered clinical problem with limited therapeutic options. Since microRNAs (miRNAs) are involved in hypoxic/ischemic events, and δ-opioid receptor (DOR) activation is known to protect against hypoxic/ischemic injury, we speculated on the involvement of DOR activation in altering miRNA expression in the heart under hypoxic conditions. The present study aimed to test our hypothesis. Methods: Male Sprague Dawley rats were exposed to hypoxia (9.5-10% O2) for 1, 5, or 10 days with or without DOR activation. The target miRNAs were selected from TaqMan low-density array (TLDA) data and were further analyzed by quantitative real-time PCR. Results: We found that: 1) hypoxia alters the miRNA expression profiles depending on the hypoxic duration; 2) DOR activation shifts miRNA expression profiles in normoxic conditions and upregulates miR-128a-3p, miR-134-5p, miR-135a, miR-193a-3p, miR-196a, miR-324-3p, and miR-338; and 3) DOR activation modifies hypoxia-induced changes in miRNA expression and increases the levels of miR-128a-3p, miR-134-5p, miR-135a, miR-193a-3p, miR-196a, miR-324-3p, miR-141, miR-200b, and miR-324-3p. For example, miR-196c-5p decreased by 50% while miR-135a-5p increased 2.9 fold after 10 days under hypoxic conditions. Moreover, DOR activation further strengthened the hypoxia-induced increase of the levels of miR-7a-5p. When DOR was activated using UFP-512, the level of miR-107-3p significantly increased 1 day after the administration of UFP-512, but gradually decreased back to normal under normoxia. Conclusion: Hypoxia significantly modifies the miRNA profile in the heart, which can be mimicked or modified by DOR activation. Defining the targeted pathways that regulate the diverse cellular and molecular functions of miRNAs may provide new insights into potential therapies for hypoxic/ischemic injury of the heart.

Abstract 324: δ-Opioid Receptor Activation Modifies Hypoxic Expression of MicroRNAs in the Rat Kidney

2012 ◽  
Vol 111 (suppl_1) ◽  
Author(s):  
Xiaozhou He ◽  
Yilin Yang ◽  
Feng Zhi ◽  
Meredith L Moore ◽  
Xuezhi Kang ◽  
...  
Keyword(s):  
Antioxidant Capacity ◽  
Opioid Receptor ◽  
Mirna Expression ◽  
Expression Profiles ◽  
Ion Homeostasis ◽  
Ischemic Injury ◽  
Receptor Activation ◽  
Pcr Analysis ◽  
Mirna Expression Profiles ◽  
Hypoxic Ischemic Injury

Cardiovascular dysfunction often causes blood/oxygen insufficiency in the kidney that is very sensitive to changes in oxygen/blood delivery. Indeed, hypoxic/ischemic kidney stress is a frequent problem in clinical settings. There is, however, no promising strategy for prevention and treatment of such injury. Since recent studies suggest that microRNAs are differentially involved in hypoxic/ischemic events and delta-opioid receptor (DOR) activation increases antioxidant capacity and protects against hypoxic/ischemic injury, we asked if DOR activation regulates microRNA expression in the kidney under hypoxic condition. We isolated microRNAs from normoxic and hypoxic rat kidneys and used the paired microRNAs for microarray analysis. Thirty-one microRNAs were selected for quantitative PCR analysis based on the microarray data. Among them, 14 microRNAs were significantly altered in response to prolonged hypoxia for 1, 5 and 10 days, DOR activation with UFP-512 (1 mg/kg/day, ip, at days 0, 4 and 8) or a combination of both. Our novel data show that 1) DOR activation shifts miRNA expression profiles in normoxic conditions; 2) hypoxia differentially alters the miRNA expression profiles depending on hypoxic durations; and 3) DOR activation modifies hypoxia-induced changes in miRNA expression. For example, 10-day hypoxia reduced the level of miR-212 by >70% (p<0.001), while DOR activation could mimic such reduction even in normoxic kidney. In contrast, the same stress increased miR-29a by >100% (p<0.05), which could be attenuated by DOR activation. These results suggest that hypoxia comprehensively modifies the microRNA profile within the kidney, which can be mimicked or modified by DOR activation. Illumination of their targeted pathways, that regulate hypoxia sensitive transcription factors, antioxidant capacity, erythropoietin, Golgi-trafficking regulator, neurexophilin, ubiquitin-mediated degradation, intracellular trafficking, scaffolding, Wnt signaling, solute channels and ion homeostasis, may provide new insights into the potential therapeutics for hypoxic/ischemic injury of the kidney.

scholarly journals Convulsant activity of a non-peptidic δ-opioid receptor agonist is not required for its antidepressant-like effects in Sprague-Dawley rats

2002 ◽  
Vol 164 (1) ◽  
pp. 42-48 ◽  
Author(s):  
Daniel Broom ◽  
Emily Jutkiewicz ◽  
John Folk ◽  
John Traynor ◽  
Kenner Rice ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Receptor Agonist ◽  
Sprague Dawley ◽  
Opioid Receptor Agonist ◽  
Sprague Dawley Rats ◽  
Δ Opioid Receptor

scholarly journals The opioid placebo analgesia is mediated exclusively through µ-opioid receptor in rat

2013 ◽  
Vol 16 (4) ◽  
pp. 849-856 ◽  
Author(s):  
Rui-Rui Zhang ◽  
Wen-Cai Zhang ◽  
Jin-Yan Wang ◽  
Jian-You Guo
Keyword(s):  
Receptor Antagonist ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Placebo Response ◽  
Anterior Cingulate ◽  
Sprague Dawley ◽  
Placebo Analgesia ◽  
Opioid Receptor Antagonist ◽  
Sprague Dawley Rats ◽  
Δ Opioid Receptor

Abstract Placebo analgesia is one of the most robust and best-studied placebo effects. Recent researches suggest that placebo analgesia activated the µ-opioid receptor signalling in the human brain. However, whether other opioid receptors are involved in the placebo analgesia remains unclear. We have previously evoked placebo responses in mice (Guo et al.2010, 2011) and these mice may serve as a model for investigating placebo analgesia. In the present study, we tried to explore the site of action and types of opioid receptors involved in placebo response. Male Sprague–Dawley rats were trained with 10 mg/kg morphine for 4 d to establish the placebo analgesia model. This placebo analgesia can be blocked by injection of 5 mg/kg dose naloxone or by microinjection with naloxone (1, 3 or 10 µg/rat) into rostral anterior cingulate cortex (rACC). Then, animals were tested after intra-rACC microinjection of d-Phe-Cys-Tyr-d-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP, a selective µ-opioid receptor antagonist) or naltrindole (NTI, a highly selective δ-opioid receptor antagonist) or nor-binaltorphimine (nor-BNI, a highly selective κ-opioid receptor antagonist). Our results showed that CTOP, but not NTI or nor-BNI, could reduce the pain threshold in placebo analgesia rats. It may be concluded that rACC is the key brain region involved in placebo analgesia and the opioid placebo analgesia is mediated exclusively through µ-opioid receptor in rat.

The K+-evoked release of [3H]acetylcholine from slices of rat globus pallidus: modulation by δ-opioid receptors

1991 ◽  
Vol 69 (3) ◽  
pp. 414-418 ◽  
Author(s):  
Bianca B. Ruzicka ◽  
Khem Jhamandas
Keyword(s):  
Globus Pallidus ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Cholinergic Neurons ◽  
Receptor Activation ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Release Of Acetylcholine ◽  
Δ Opioid Receptor ◽  
Tritium Release

Previous investigations have shown that the activation of δ-opioid receptors depresses the release of acetylcholine (ACh) in the rat caudate putamen. This finding raised the possibility that the release of ACh is similarly modulated in the globus pallidus, a region containing a distinct population of cholinergic neurons and enriched in enkephalinergic nerve terminals. In the present study the pallidal release of ACh was characterized and the effects of δ-opioid receptor activation on this release were examined. The results show that this release is stimulated by high K+ in a concentration- and Ca2+-dependent manner. D-Pen2,L-Pen5-enkephalin (0.1 – 10 μM), a selective δ-opioid receptor agonist, produced a dose-related inhibition of the 25 mM K+-evoked tritium release. The maximal inhibitory effect, representing a 34% decrease in the K+-induced tritium release, was observed at a concentration of 1 μM. This opioid effect was attenuated by the selective δ-opioid receptor antagonist, ICI 174864 (1 μM). These findings support the role of a δ-opioid receptor in the modulation of ACh release in the rat globus pallidus.Key words: globus pallidus, acetylcholine, enkephalin, release.

Mineralocorticoid Receptor Activation by Aldosterone or Corticosterone Induces Hypertension, Myocardial Infarction and Proteinuria

Hypertension ◽  
2000 ◽  
Vol 36 (suppl_1) ◽  
pp. 723-723
Author(s):  
Qing-Feng Tao ◽  
Diego Martinez vasquez ◽  
Ricardo Rocha ◽  
Gordon H Williams ◽  
Gail K Adler
Keyword(s):  
Myocardial Infarction ◽  
Drinking Water ◽  
Mineralocorticoid Receptor ◽  
Critical Role ◽  
Weight Ratio ◽  
Myocardial Necrosis ◽  
Receptor Activation ◽  
Control Group ◽  
Sprague Dawley ◽  
Sprague Dawley Rats

P165 Aldosterone through its interaction with the mineralocorticoid receptor (MR) plays a critical role in the development of hypertension and cardiovascular injury (CVI). Normally, MR is protected by 11β-hydroxysteroid dehydrogenase (11β-HSD) which inactivates glucocorticoids preventing their binding to MR. We hypothesis that if activation of MR by either aldosterone or glucocorticoids induces hypertension and CVI, then the inhibition of 11β-HSD with glycyrrhizin (GA), a natural inhibitor of 11β-HSD, should induce damage similar to that observed with aldosterone. Sprague-Dawley rats were uninephrectomized, and treated for 4 weeks with 1% NaCl (in drinking water) for the control group, 1% NaCl + aldosterone infusion (0.75 μg/h), or 1% NaCl + GA (3.5 g/l in drinking water). After 4 weeks, aldosterone and GA caused significant increases in blood pressure compared to control rats ([mean ± SEM] 211± 9, 205 ± 12, 120 ± 9 mmHg, respectively, p<0.001). Both aldosterone- and GA-treated rats had a significant increase in proteinuria (152.2 ± 8.7 and 107.7 ± 19.5 mg/d, respectively) versus controls (51.2 ± 9.5 mg/d). There was a significant increase (p<0.001) in heart to body weight ratio in the rats treated with aldosterone or GA compared with control (3.92 ± 0.10, 3.98 ± 0.88, and 3.24 ± 0.92 mg/g, respectively). Hearts of GA and aldosterone treated rats showed similar histological changes consisting of biventricular myocardial necrosis and fibrinoid necrosis of small coronary arteries and arterioles. These data suggests that in rodents activation of MR by either aldosterone or corticosterone leads to severe hypertension, vascular injury, proteinuria and myocardial infarction. Thus, 11β-HSD plays an important role in protecting the organism from injury.

scholarly journals Selected Contribution: Phrenic long-term facilitation requires 5-HT receptor activation during but not following episodic hypoxia

2001 ◽  
Vol 90 (5) ◽  
pp. 2001-2006 ◽  
Author(s):  
D. D. Fuller ◽  
A. G. Zabka ◽  
T. L. Baker ◽  
G. S. Mitchell
Keyword(s):  
Receptor Antagonist ◽  
Phrenic Nerve ◽  
Receptor Activation ◽  
Sprague Dawley ◽  
Nerve Activity ◽  
Sprague Dawley Rats ◽  
Episodic Hypoxia ◽  
Baseline Levels ◽  
Long Term Facilitation

Episodic hypoxia evokes a sustained augmentation of respiratory motor output known as long-term facilitation (LTF). Phrenic LTF is prevented by pretreatment with the 5-hydroxytryptamine (5-HT) receptor antagonist ketanserin. We tested the hypothesis that 5-HT receptor activation is necessary for the induction but not maintenance of phrenic LTF. Peak integrated phrenic nerve activity (∫Phr) was monitored for 1 h after three 5-min episodes of isocapnic hypoxia (arterial Po 2 = 40 ± 2 Torr; 5-min hyperoxic intervals) in four groups of anesthetized, vagotomized, paralyzed, and ventilated Sprague-Dawley rats [ 1) control ( n = 11), 2) ketanserin pretreatment (2 mg/kg iv; n = 7), and ketanserin treatment 0 and 45 min after episodic hypoxia ( n = 7 each)]. Ketanserin transiently decreased ∫Phr, but it returned to baseline levels within 10 min. One hour after episodic hypoxia, ∫Phr was significantly elevated from baseline in control and in the 0- and 45-min posthypoxia ketanserin groups. Conversely, ketanserin pretreatment abolished phrenic LTF. We conclude that 5-HT receptor activation is necessary to initiate (during hypoxia) but not maintain (following hypoxia) phrenic LTF.

scholarly journals TAN-67, a δ1-opioid receptor agonist, reduces infarct size via activation of Gi/oproteins and KATPchannels

1998 ◽  
Vol 274 (3) ◽  
pp. H909-H914 ◽  
Author(s):  
Jo El J. Schultz ◽  
Anna K. Hsu ◽  
Hiroshi Nagase ◽  
Garrett J. Gross
Keyword(s):  
Infarct Size ◽  
Opioid Receptor ◽  
Opioid Receptors ◽  
Coronary Artery Occlusion ◽  
Receptor Activation ◽  
Artery Occlusion ◽  
Cardioprotective Effect ◽  
Area At Risk ◽  
Opioid Receptor Agonist ◽  
Δ Opioid Receptor

We have previously shown that delta (δ)-opioid receptors, most notably δ1, are involved in the cardioprotective effect of ischemic preconditioning (PC) in rats; however, the mechanism by which δ-opioid receptor-induced cardioprotection is mediated remains unknown. Therefore, we hypothesized that several of the known mediators of ischemic PC such as the ATP-sensitive potassium (KATP) channel and Gi/oproteins are involved in the cardioprotective effect produced by δ1-opioid receptor activation. To address these possibilities, anesthetized, open-chest Wistar rats were randomly assigned to five groups. Control animals were subjected to 30 min of coronary artery occlusion and 2 h of reperfusion. To demonstrate that stimulating δ1-opioid receptors produces cardioprotection, TAN-67, a new selective δ1-agonist, was infused for 15 min before the long occlusion and reperfusion periods. In addition, one group received 7-benzylidenenaltrexone (BNTX), a selective δ1-antagonist, before TAN-67. To study the involvement of KATPchannels or Gi/oproteins in δ1-opioid receptor-induced cardioprotection, glibenclamide (Glib), a KATPchannel antagonist, or pertussis toxin (PTX), an inhibitor of Gi/oproteins, was administered before TAN-67. Infarct size (IS) as a percentage of the area at risk (IS/AAR) was determined by tetrazolium stain. TAN-67 significantly reduced IS/AAR as compared with control (56 ± 2 to 27 ± 5%, n = 5, P < 0.05). The cardioprotective effect of TAN-67 was completely abolished by BNTX, Glib, and PTX (51 ± 3, 53 ± 5, and 61 ± 4%, n = 6 for each group, respectively). These results are the first to suggest that stimulating the δ1-opioid receptor elicits a cardioprotective effect that is mediated via Gi/oproteins and KATPchannels in the intact rat heart.

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