δ2 opioid receptor subtype on human vascular endothelium uncouples morphine stimulated nitric oxide release

Stefano, George B.; Hughes, Thomas K.; Bilfinger, Thomas V.

doi:10.1016/s0167-5273(98)00035-7

Cited by 26 publications

(7 citation statements)

References 25 publications

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“…Although we currently have no evidence that formation of ROS occurs in animals pretreated 24 hours with d opioids before HS, it is possible that Delt-D var interacts with mitochondria and/or modifies sarcolemmal K ATP channel activity by modulation of redox-sensitive or metabolic mechanisms that trigger ischemic protection and improve the recompensatory phase of hemorrhage. Recent studies 35,36 have shown that d 2 opioid receptors are present throughout the vascular endothelium, where they have been shown to block morphine-stimulated nitric oxide release and NO-mediated vasodilation, and that d opioid receptor activation is involved in regulation of contractile tone resulting in vasoconstriction. Although the latter studies were not conducted utilizing an HS model, they nevertheless raise the possibility that exogenously administered d opioids given immediately after hemorrhage or 24-48 hours before hemorrhage could initiate vasopressor effects during HS that are similar to those seen with vasopressin infusion.…”

Section: Discussionmentioning

confidence: 99%

“…In the vasopressin studies, vasopressin, but not fluid resuscitation, increased MAP and significantly improved survival rates in a pig liver trauma model with otherwise lethal HS. 35 This was believed to occur because of a profound vasopressin-mediated peripheral vasoconstriction via V1 receptors in the vasculature, which shifts blood primarily from the skeletal muscle, skin, and splanchnic bed to heart and brain. 37 It has also been demonstrated in both cardiopulmonary resuscitation and HS studies that vasopressin temporarily impairs mesenteric artery and, subsequently, portal vein blood flow, while arterial reperfusion of the liver and kidneys is restored.…”

Section: Discussionmentioning

confidence: 99%

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24‐Hour Pretreatment with δ Opioid Enhances Survival from Hemorrhagic Shock

Oeltgen

Govindaswami

Witzke

2006

Academic Emergency Medicine

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Objectives: d opioids have been shown to confer ischemic preconditioning and pharmacologic ischemic preconditioning to the myocardium. However, their role in providing extended pharmacologic ischemic preconditioning in hemorrhagic shock has not been explored. The authors examined the effects of 24-hour preinfusions of a selective d opioid receptor agonist, Deltorphin-D variant (Delt-D var ), on hemodynamic stability and duration of survival in a rat model of severe hemorrhagic shock.Methods: Conscious Sprague-Dawley rats with indwelling catheters were hemorrhaged at a rate of 3.18 mL/l00 g over 20 minutes. Twenty-four hours before hemorrhage, the control group (n = 14) was infused with 1.0 mL lactated Ringer's solution, and the Delt-D var -treated group (n = 22) was infused with 5.0 mg/kg Delt-D var in 1.0 mL lactated Ringer's solution. Rats were continuously monitored for heart rate (HR), mean arterial pressure, and four-hour survival rates. Plasma lactate levels were determined at the beginning of hemorrhage and the end of hemorrhage.Results: At 240 minutes, only one of 14 controls (7.1%) survived, while 16 (72.7%) of the 22 experimental rats survived. No significant differences in heart rate between controls and Delt-D var -treated rats were noted. Increases in mean arterial pressure of Delt-D var -treated rats at the beginning of hemorrhage and at the end of hemorrhage were found to be significant (p < 0.05). At 240 minutes, heart rate and mean arterial pressure were not different between the single surviving control and the Delt-D var group. At the end of hemorrhage, lactate levels in the Delt-D var -treated group were 8.5 (AE0.5) mmol/L versus 10.8 (AE0.6) mmol/L (p < 0.05) in the control group.Conclusions: Twenty-four-hour pretreatment with Delt-D var decreases plasma lactate levels and improves hemodynamic stability and survival during hemorrhagic shock. The use of d-specific opioids may improve survival from hemorrhagic shock and have clinical utility in providing ischemic protection in scenarios of planned ischemia.ACADEMIC EMERGENCY MEDICINE 2006; 13:127-133 ª

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

24‐Hour Pretreatment with δ Opioid Enhances Survival from Hemorrhagic Shock

Oeltgen

Govindaswami

Witzke

2006

Academic Emergency Medicine

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“…These reports also demonstrate, on a pharmacological and biochemical basis, that the corresponding receptors are present as well, along with the intracellular second messenger communication processes [23][24][25][26]. Opioid peptides and opiate alkaloids (e.g., enkephalins, morphine) are also present with their respective receptors and biosynthetic pathways [27][28][29][30][31]. From a neuroimmune perspective, the same chemical messengers and their receptors have been found on invertebrate immunocytes, including nitric oxide coupling, allowing neurons to communicate with the immune cells, including microglia [32][33][34][35][36][37][38][39][40][41][42] (Figures 1 and 2).…”

Section: Common Set Of Shared Signal Moleculesmentioning

confidence: 92%

Evolutionary Perspective on Microglial/Neuronal Coupling with Special Relevance to Psychiatric Illnesses

Stefano¹,

Kream²

2015

J Psychiatry

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Journal of Psychiatry AbstractMicroglia have selectively evolved as a morphologically and chemically distinct class of immuno-competent CNS resident cells with potent bidirectional signaling capabilities linked to induction of a macrophage-like phenotype following metabolic, microbiological, or viral insults. It has been empirically determined that a conserved set of shared chemical messengers connects a communication network mediating reciprocal exchange of regulatory information between immune, central nervous, and neuroendocrine systems. From an evolutionary perspective, the pluripotent neuro-protective capabilities of invertebrate microglia have been extended and amplified in classes of mammalian microglia. The state-dependent plasticity of microglia has provoked considerable empirical investigation into their functional/regulatory roles in mediating innate immune surveillance and neural protection within the CNS. Upon pathophysiological dysregulation, aberrant microglial activities may provide significant contributory factors in the etiology and persistence of major neurological, degenerative, and psychiatric disorders. Within this context, invertebrate microglia appear to represent highly appropriate model systems to investigate underlying cellular and molecular mechanisms involved in higher order neuroimmune regulation of multiple CNS activities by mammalian microglia.

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“…However, in 1995, the μ 3 subtype of this receptor was detected in the coronary microvascular's endothelial cells . This group of researchers also established that endothelial cells express a δ 2 OR subtype . Vascular smooth muscle cells also appeared to express δ OR .…”

Section: Localization Of Opioid Receptors Involved In Regulation Of Hmentioning

confidence: 96%

Prospects for Creation of Cardioprotective and Antiarrhythmic Drugs Based on Opioid Receptor Agonists

Maslov

Khaliulin

Oeltgen

et al. 2016

Medicinal Research Reviews

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It has now been demonstrated that the μ, δ1, δ2, and κ1 opioid receptor (OR) agonists represent the most promising group of opioids for the creation of drugs enhancing cardiac tolerance to the detrimental effects of ischemia/reperfusion (I/R). Opioids are able to prevent necrosis and apoptosis of cardiomyocytes during I/R and improve cardiac contractility in the reperfusion period. The OR agonists exert an infarct‐reducing effect with prophylactic administration and prevent reperfusion‐induced cardiomyocyte death when ischemic injury of heart has already occurred; that is, opioids can mimic preconditioning and postconditioning phenomena. Furthermore, opioids are also effective in preventing ischemia‐induced arrhythmias.

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δ2 opioid receptor subtype on human vascular endothelium uncouples morphine stimulated nitric oxide release

Cited by 26 publications

References 25 publications

24‐Hour Pretreatment with δ Opioid Enhances Survival from Hemorrhagic Shock

24‐Hour Pretreatment with δ Opioid Enhances Survival from Hemorrhagic Shock

Evolutionary Perspective on Microglial/Neuronal Coupling with Special Relevance to Psychiatric Illnesses

Prospects for Creation of Cardioprotective and Antiarrhythmic Drugs Based on Opioid Receptor Agonists

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