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.

Activation of δ- and κ-opioid receptors by opioid peptides protects cardiomyocytes via KATP channels

2003 ◽  
Vol 285 (3) ◽  
pp. H1032-H1039 ◽  
Author(s):  
Zhiping Cao ◽  
Lijuan Liu ◽  
Donna M. Van Winkle
Keyword(s):  
Cell Death ◽  
Opioid Receptors ◽  
Opioid Peptides ◽  
Trypan Blue ◽  
Area Under The Curve ◽  
Katp Channels ◽  
Opioid Peptide ◽  
Adult Rabbit ◽  
Receptor Specificity ◽  
Selective Antagonist

To examine the receptor specificity and the mechanism of opioid peptide-induced protection, we examined freshly isolated adult rabbit cardiomyocytes subjected to simulated ischemia. Cell death as a function of time was assessed by trypan blue permeability. Dynorphin B (DynB) and Met5-enkephalin (ME) limitation of cell death (expressed as area under the curve) was sensitive to blockade by naltrindole (NTI, a δ-selective antagonist) and 5′-guanidinyl-17-(cyclopropylmethyl)-6,7-dehydro-4,5α-epoxy-3,14-dihydroxy-6,7-2′,3′-indolomorphinan (GNTI dihydrochloride, a κ-selective antagonist): 85.7 ± 2.7 and 142.9 ± 2.7 with DynB and DynB + NTI, respectively ( P < 0.001), 94.1 ± 4.2 and 164.5 ± 7.3 with DynB and DynB + GNTI, respectively ( P < 0.001), 111.9 ± 7.0 and 192.1 ± 6.4 with ME and ME + NTI, respectively ( P < 0.001), and 120.2 ± 4.3 and 170.0 ± 3.3 with ME and ME + GNTI, respectively ( P < 0.001). Blockade of ATP-sensitive K+ channels eliminated DynB- and ME-induced protection: 189.6 ± 5.4 and 139.0 ± 5.4 for control and ME, respectively ( P < 0.001), and 210 ± 5.9 and 195 ± 6.1 for 5-HD and ME + 5-HD, respectively ( P < 0.001); 136.0 ± 5.7 and 63.4 ± 5.4 for control and ME, respectively ( P < 0.001), and 144.6 ± 4.5 and 114.6 ± 7.7 for HMR-1098 and ME + HMR-1098, respectively ( P < 0.01); 189.6 ± 5.4 and 139.0 ± 5.4 for control and ME, respectively ( P < 0.001), and 210 ± 5.9 and 195 ± 6.1 for 5-HD and ME + 5-HD, respectively ( P < 0.001); and 136.0 ± 5.7 and 63.4 ± 5.4 for control and ME, respectively ( P < 0.001), and 144.6 ± 4.5 and 114.6 ± 7.7 for HMR-1098 and ME + HMR-1098, respectively ( P < 0.01). We conclude that opioid peptide-induced cardioprotection is mediated by δ- and κ-receptors and involves sarcolemmal and mitochondrial ATP-sensitive K+ channels.

Role of endogenous opioid peptides in protection of ischemic preconditioning in rat small intestine

Life Sciences ◽  
2001 ◽  
Vol 68 (9) ◽  
pp. 1013-1019 ◽  
Author(s):  
Yi Zhang ◽  
Yu-Xiu Wu ◽  
Yi-Bin Hao ◽  
Yin Dun ◽  
Shuan-Ping Yang
Keyword(s):  
Small Intestine ◽  
Ischemic Preconditioning ◽  
Opioid Peptides ◽  
Rat Small Intestine ◽  
Endogenous Opioid Peptides ◽  
Endogenous Opioid

Types of opioid receptors: relation to antinociception

1985 ◽  
Vol 308 (1136) ◽  
pp. 291-297 ◽  
Keyword(s):  
Nervous System ◽  
Opioid Receptors ◽  
Opioid Peptides ◽  
Binding Sites ◽  
Endogenous Opioid Peptides ◽  
Endogenous Opioid ◽  
Narcotic Analgesics ◽  
High Concentrations ◽  
P Type ◽  
Μ Receptor

The endogenous opioid peptides are derived from three large precursors. Pro-opiocortin and proenkephalin yield [Met]enkephalin, carboxy-extended [Met]enkephalins and [Leu]enkephalin. The fragments of prodynorphin are all carboxy-extended [Leu]- enkephalins. Three approaches are of importance for an analysis of the physiological functions of the different endogenous opioid peptides. First, since these peptides interact with more than one of the μ-, δ- and K-binding sites and thus with their receptors, it is necessary to synthesize peptides or non-peptides, which bind to only one of the sites. As far as narcotic analgesics are concerned, morphine fulfils these conditions since it interacts almost exclusively with the μ-receptor. Secondly, antagonists are required that are selective for only one of the opioid receptors, even when used in high concentrations. Finally, it is important to find circumscribed areas in the nervous system that possess only one type of opioid receptor. It is now known that in the rabbit cerebellum the opioid receptors are almost exclusively of the p-type whereas in the guinea-pig cerebellum they are almost exclusively of the K-type.

Regulation of Opioid Receptors by Their Endogenous Opioid Peptides

2021 ◽  
Author(s):  
Achla Gupta ◽  
Srinivas Gullapalli ◽  
Hui Pan ◽  
Dinah L. Ramos-Ortolaza ◽  
Michael D. Hayward ◽  
...  
Keyword(s):  
Opioid Receptors ◽  
Opioid Peptides ◽  
Endogenous Opioid Peptides ◽  
Endogenous Opioid
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