Opioid Receptors, KATP Channels and Ischemic Preconditioning

1997 ◽  
pp. 125-131
Author(s):  
Garrett J. Gross ◽  
Jo El Schultz
Keyword(s):  
Opioid Receptors ◽  
Ischemic Preconditioning ◽  
Katp Channels

Met5-enkephalin protects isolated adult rabbit cardiomyocytes via δ-opioid receptors

1999 ◽  
Vol 277 (6) ◽  
pp. H2442-H2450 ◽  
Author(s):  
Yasushi Takasaki ◽  
Roger A. Wolff ◽  
Grace L. Chien ◽  
Donna M. van Winkle
Keyword(s):  
Cell Death ◽  
Opioid Receptors ◽  
Ischemic Preconditioning ◽  
Opioid Peptides ◽  
Trypan Blue ◽  
Adult Rabbit ◽  
Endogenous Opioid Peptides ◽  
Endogenous Opioid ◽  
Simulated Ischemia ◽  
Hypoxic Incubation

In rats and rabbits, endogenous opioid peptides participate in ischemic preconditioning. However, it is not known which endogenous opioid(s) can trigger cardioprotection. We examined preconditioning-induced and opioid-induced limitation of cell death in isolated, calcium-tolerant, adult rabbit cardiomyocytes. Cells were subjected to simulated ischemia by pelleting and normothermic hypoxic incubation. Preconditioning was elicited with 15 min of simulated ischemia followed by 15 min of resuspension and reoxygenation. All cells underwent 180 min of simulated ischemia. Cell death was assessed by trypan blue permeability. Morphine protected cells, as did preconditioning; naloxone blocked the preconditioning-induced protection. Exogenous Met5-enkephalin (ME) induced protection, but exogenous β-endorphin did not. ME-induced protection was blocked by the δ-selective antagonist naltrindole. Additionally, two other proenkephalin products, Leu5-enkephalin and Met5-enkephalin-Arg-Phe, provided protection equipotent to ME. These data suggest that one or more proenkephalin products interact with δ-opioid receptors to endogenously trigger opioid-mediated protection.

κ- but not δ-opioid receptors mediate effects of ischemic preconditioning on both infarct and arrhythmia in rats

2001 ◽  
Vol 280 (1) ◽  
pp. H384-H391 ◽  
Author(s):  
Guan-Ying Wang ◽  
Song Wu ◽  
Jian-Ming Pei ◽  
Xiao-Chun Yu ◽  
Tak-Ming Wong
Keyword(s):  
Infarct Size ◽  
Opioid Receptors ◽  
Ischemic Preconditioning ◽  
Antiarrhythmic Action ◽  
Perfused Rat Heart ◽  
Calphostin C ◽  
Kinase C ◽  
Series Of Experiments ◽  
Pkc Inhibitors

Two series of experiments were performed in the isolated perfused rat heart to determine the role of κ- and δ-opioid receptors (OR) in cardioprotection of ischemic preconditioning (IP). In the first series of experiments, it was found that IP with two cycles of 5-min regional ischemia followed by 5-min reperfusion each reduced infarct size induced by 30-min ischemia, and the ameliorating effect of IP on infarct was attenuated with blockade of either 5 × 10−6 mol/l nor-binaltorphimine (nor-BNI), a selective κ-OR antagonist, or 5 × 10−6 mol/l naltrindole (NTD), a selective δ-OR antagonist. The second series showed that U50,488H, a selective κ-OR agonist, ord-Ala2-d-leu5-enkephalin (DADLE), a selective δ-OR agonist, dose dependently reduced the infarct size induced by ischemia, which mimicked the effects of IP. The effect of 10−5 mol/l U50,488H on infarct was significantly attenuated by blockade of protein kinase C (PKC) with specific PKC inhibitors, 5 × 10−6 mol/l chelerythrine or 8 × 10−7 mol/l calphostin C, as well as by blockade of ATP-sensitive K+ (KATP) channels with blockers of the channel, 10−5 mol/l glibenclamide or 10−4 mol/l 5-hydroxydecanoate. IP also reduced arrhythmia induced by ischemia. Nor-BNI, but not NTD, attenuated, while U50,488H, but not DADLE, mimicked the antiarrhythmic action of IP. In conclusion, the present study has provided first evidence that κ-OR mediates the ameliorating effects of IP on infarct and arrhythmia induced by ischemia, whereas δ-OR mediates the effects only on infarct. Both PKC and KATP channels mediate the effect of activation of κ-OR on infarct.

Differential role of sarcolemmal and mitochondrial KATP channels in adenosine-enhanced ischemic preconditioning

2000 ◽  
Vol 279 (6) ◽  
pp. H2694-H2703 ◽  
Author(s):  
Yoshiya Toyoda ◽  
Ingeborg Friehs ◽  
Robert A. Parker ◽  
Sidney Levitsky ◽  
James D. McCully
Keyword(s):  
Infarct Size ◽  
Functional Recovery ◽  
Ischemic Preconditioning ◽  
Channel Blocker ◽  
Katp Channels ◽  
Size Reduction ◽  
Ischemia And Reperfusion ◽  
Infarct Size Reduction ◽  
Mitochondrial Katp Channels

Adenosine-enhanced ischemic preconditioning (APC) extends the protection afforded by ischemic preconditioning (IPC) by both significantly decreasing infarct size and significantly enhancing postischemic functional recovery. The purpose of this study was to determine whether APC is modulated by ATP-sensitive potassium (KATP) channels and to determine whether this modulation occurs before ischemia or during reperfusion. The role of KATP channels before ischemia (I), during reperfusion (R), or during ischemia and reperfusion (IR) was investigated using the nonspecific KATP blocker glibenclamide (Glb), the mitochondrial (mito) KATP channel blocker 5-hydroxydecanoate (5-HD), and the sarcolemmal (sarc) KATPchannel blocker HMR-1883 (HMR). Infarct size was significantly increased ( P < 0.05) in APC hearts with Glb-I, Glb-R, and 5-HD-I treatment and partially with 5-HD-R. Glb-I and Glb-R treatment significantly decreased APC functional recovery ( P < 0.05 vs. APC), whereas 5-HD-I and 5-HD-R had no effect on APC functional recovery. HMR-IR significantly decreased postischemic functional recovery ( P < 0.05 vs. APC) but had no effect on infarct size. These data indicate that APC infarct size reduction is modulated by mitoKATP channels primarily during ischemia and suggest that functional recovery is modulated by sarcKATP channels during ischemia and reperfusion.

KATP channels and memory of ischemic preconditioning in dogs: synergism between adenosine and KATP channels

1997 ◽  
Vol 272 (1) ◽  
pp. H334-H342 ◽  
Author(s):  
Z. Yao ◽  
T. Mizumura ◽  
D. A. Mei ◽  
G. J. Gross
Keyword(s):  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Katp Channels ◽  
Canine Heart ◽  
Ischemic Insult ◽  
Area At Risk ◽  
Adenosine Receptor Antagonist ◽  
Anesthetized Dogs ◽  
Drug Free ◽  
Occlusion Period

Results from numerous studies have shown that there is an important link between adenosine A1 receptors and ATP-sensitive potassium (KATP) channels in mediating the cardioprotective effects of ischemic preconditioning (PC). The major aim of the present study was to determine whether occupation of A1 receptors and/or the opening of KATP channels is involved in the time delay between the PC stimulus and the prolonged ischemic insult or the “memory” of PC to reduce infarct size. Barbital sodium-anesthetized dogs were subjected to 1 h of left anterior descending coronary artery (LAD) occlusion followed by 4 h of reperfusion. Ischemic PC was elicited by 10 min of LAD occlusion followed by 1 h of reperfusion (1-h memory) before the 1-h occlusion period. Either adenosine (800 g/min), bimakalim (3 g/min), a combination of two lower doses of each agent (400 g/min of adenosine and 0.3 g/min of bimakalim), or an equivalent volume of saline was infused into the LAD for 10 min followed by a 1-h drug-free period before the 1-h ischemic insult. In another series, glibenclamide, 8-cyclopentyl-1,3-dipropylxanthine (a selective A1-receptor blocker), or PD-115199 (a nonselective adenosine-receptor antagonist) was administered 50 min after ischemic PC (10 min before the 1-h occlusion period). Infarct size (IS) was expressed as a percentage of the area at risk. PC with 1 h of reperfusion resulted in a marked reduction in IS (8.1 +/- 6.5 vs. 29.8 +/- 5.8% in control dogs). Administration of adenosine or bimakalim followed by a 1-h drug-free period had no effect on IS; however, the simultaneous administration of adenosine and bimakalim resulted in a marked decrease in IS (11.5 +/- 2.7%). One hour after ischemic PC, administration of glibenclamide blocked the protective effect of ischemic PC, whereas 8-cyclopentyl-1,3-dipropylxanthine or PD-115199 did not affect it. These results provide evidence that the opening of myocardial KATP channels may play an important role in the memory of ischemic PC in the canine heart and also suggest that adenosine and the KATP channel may have a synergistic interaction that is important for the memory phase of PC.

Mitochondrial KATP channels are possible triggers of ischemic preconditioning protective effect against reperfusion arrhythmias

2002 ◽  
Vol 34 (6) ◽  
pp. A44
Author(s):  
Danina M. Muntean ◽  
Alexandru Cristescu ◽  
Ovidiu Fira-Mladinescu ◽  
Dan Mihaicuta ◽  
Daniel Lighezan
Keyword(s):  
Protective Effect ◽  
Ischemic Preconditioning ◽  
Katp Channels ◽  
Reperfusion Arrhythmias ◽  
Mitochondrial Katp Channels

scholarly journals Protein Kinase C and Gi/o Proteins Are Involved in Adenosine- and Ischemic Preconditioning—Mediated Renal Protection

2001 ◽  
Vol 12 (2) ◽  
pp. 233-240 ◽  
Author(s):  
H. THOMAS LEE ◽  
CHARLES W. EMALA
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Opioid Receptors ◽  
Pertussis Toxin ◽  
Ischemic Preconditioning ◽  
Clinical Problem ◽  
Protective Effects ◽  
Renal Protection ◽  
Kinase C

Abstract. Renal ischemic reperfusion (IR) injury is a significant clinical problem in anesthesia and surgery. Recently, it was demonstrated that both renal ischemic preconditioning (IPC) and systemic adenosine pretreatment protect against renal IR injury. In cardiac IPC, pertussis toxin-sensitive G-proteins (i.e., Gi/o), protein kinase C (PKC), and ATP-sensitive potassium (K+ATP) channels are implicated in this protective signaling pathway. The aim of this study was to elucidate the signaling pathways that are responsible for renal protection mediated by both IPC and adenosine pretreatment. In addition, because A1 adenosine receptor antagonist failed to block renal IPC, whether activation of bradykinin, muscarinic, or opioid receptors can mimic renal IPC was tested because these receptors have been implicated in cardiac IPC. Rats were acutely pretreated with chelerythrine or glibenclamide, selective blockers of PKC and K+ATP channels, respectively, before IPC or adenosine pretreatment. Some rats were pretreated with pinacidil (K+ATP channel opener), bradykinin, methacholine, or morphine before renal ischemia. Twenty-four h later, plasma creatinine was measured. Separate groups of rats received pertussis toxin intraperitoneally 48 h before being subjected to the above protective protocols. IPC and adenosine pretreatment protected against renal IR injury. Pretreatment with pertussis toxin and chelerythrine abolished the protective effects of both renal IPC and adenosine. However, glibenclamide pretreatment had no effect on either renal IPC or adenosine-induced renal protection, indicating no apparent role for K+ATP channels. Moreover, pinacidil, bradykinin, methacholine, and morphine failed to protect renal function. Therefore, the conclusion is that cellular signal transduction pathways of renal IPC and adenosine pretreatment in vivo involve Gi/o proteins and PKC but not K+ATP channels. Unlike cardiac IPC, bradykinin, muscarinic, and opioid receptors do not mediate renal IPC.

KATP Channels Mediate the Effect of Ischemic Preconditioning on Free Radical Production in a Rabbit Heart Model

2002 ◽  
Vol 96 (Sup 2) ◽  
pp. A629
Author(s):  
Yaacov Gozal ◽  
Jacob Raphael ◽  
Mordechai Chevion ◽  
Benjamin Drenger
Keyword(s):  
Free Radical ◽  
Ischemic Preconditioning ◽  
Katp Channels ◽  
Rabbit Heart ◽  
Heart Model ◽  
Free Radical Production ◽  
Radical Production

KATP channels in rat heart: blockade of ischemic and acetylcholine-mediated preconditioning by glibenclamide

1996 ◽  
Vol 271 (1) ◽  
pp. H23-H28 ◽  
Author(s):  
Y. Z. Qian ◽  
J. E. Levasseur ◽  
K. Yoshida ◽  
R. C. Kukreja
Keyword(s):  
Infarct Size ◽  
Ischemic Preconditioning ◽  
Rat Heart ◽  
Katp Channel ◽  
Katp Channels ◽  
Ischemia And Reperfusion ◽  
Area At Risk ◽  
Specific Antagonist ◽  
Percent Area

The objective of this study was to examine if the opening of ATP-sensitive K+ (KATP) channels play an important role in ischemic preconditioning (PC) in the rat heart. A second goal was to test the role of acetylcholine (ACh) in mimicking PC and test if it could be blocked by KATP antagonist. Glibenclamide, a specific antagonist of the KATP channel, was given as two doses of 0.3 mg/kg each at 60 and 30 min before PC. Six groups of rats were subjected to ischemia and reperfusion (I/R) using these protocols: 1) control (I/R), 30-min ischemia followed by 90-min reperfusion (n = 6 rats); 2) preconditioned hearts given 5-min ischemia 10 min before I/R (n = 9 rats); 3) glibenclamide (0.3 mg/kg) treatment 60 and 30 min before PC (n = 13 rats); 4) glibenclamide treatment before I/R (n = 15 rats); 5) ACh infusion for 5 min (18 micrograms/ml) at a rate of 0.15 ml/min followed by equilibration for 10 min before I/R, n = 13 rats; and 6) glibenclamide treatment before ACh infusion followed by I/R (n = 11 rats). Preconditioning reduced the infarcted area (expressed as percent area at risk) from 42.0 +/- 4.4% in control to 8.7 +/- 6% (mean +/- SE, P < 0.05). Glibenclamide blocked the protection conferred by PC (39.1 +/- 4.5%, P < 0.05) without having a significant effect on control nonpreconditioned hearts. ACh infusion in lieu of PC also reduced infarct size to 25.0 +/- 5.63% (P < 0.05 compared with control), which was again blocked by glibenclamide (44.2 +/- 5.0%, P < 0.05). The data suggest that opening of KATP channels for ischemic and ACh-mediated preconditioning is also important in the rat heart.

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