Anesthetic Potency and Influence of Morphine and Sevoflurane on Respiration in μ-Opioid Receptor Knockout Mice

2001 ◽  
Vol 94 (5) ◽  
pp. 824-832 ◽  
Author(s):  
Albert Dahan ◽  
Elise Sarton ◽  
Luc Teppema ◽  
Cees Olievier ◽  
Diederik Nieuwenhuijs ◽  
...  
Keyword(s):  
Carbon Dioxide ◽  
Opioid Receptor ◽  
Carbon Dioxide Concentration ◽  
Control Of Breathing ◽  
Opioid System ◽  
Whole Body ◽  
Wild Type ◽  
Exon 2 ◽  
Mu Opioid ◽  
Anesthetic Potency

Background The involvement of the mu-opioid receptor (muOR) system in the control of breathing, anesthetic potency, and morphine- and anesthesia-induced respiratory depression was investigated in mice lacking the muOR. Methods Experiments were performed in mice lacking exon 2 of the muOR gene (muOR-/-) and their wild-type littermates (muOR+/+). The influence of saline, morphine, naloxone, and sevoflurane on respiration was measured using a whole body plethysmographic method during air breathing and elevations in inspired carbon dioxide concentration. The influence of morphine and naloxone on anesthetic potency of sevoflurane was determined by tail clamp test. Results Relative to wild-type mice, muOR-deficient mice displayed approximately 15% higher resting breathing frequencies resulting in greater resting ventilation levels. The slope of the ventilation-carbon dioxide response did not differ between genotypes. In muOR+/+ but not muOR-/- mice, a reduction in resting ventilation and slope, relative to placebo, was observed after 100 mg/kg morphine. Naloxone increased resting ventilation and slope in both genotypes. Sevoflurane at 1% inspired concentration induced similar reductions in resting ventilation and slope in the two genotypes. Anesthetic potency was 20% lower in mutant relevant to wild-type mice. Naloxone and morphine caused an increase and decrease, respectively, in anesthetic potency in muOR+/+ mice only. Conclusions The data indicate the importance of the endogenous opioid system in the physiology of the control of breathing with only a minor role for the muOR. The muOR gene is the molecular site of action of the respiratory effects of morphine. Anesthetic potency is modulated by the endogenous mu-opioid system but not by the kappa- and delta-opioid systems.

scholarly journals Regulation of breathing pattern by IL-10

2019 ◽  
Vol 317 (1) ◽  
pp. R190-R202 ◽  
Author(s):  
Charoula Eleni Giannakopoulou ◽  
Adamantia Sotiriou ◽  
Maria Dettoraki ◽  
Michael Yang ◽  
Fotis Perlikos ◽  
...  
Keyword(s):  
Tidal Volume ◽  
Minute Ventilation ◽  
Control Of Breathing ◽  
Neonatal Rat ◽  
Whole Body ◽  
Wild Type ◽  
Rapid Shallow Breathing Index ◽  
Regulation Of Breathing ◽  
Shallow Breathing

Proinflammatory cytokines like interleukin-1β (IL-1β) affect the control of breathing. Our aim is to determine the effect of the anti-inflammatory cytokine IL-10 οn the control of breathing. IL-10 knockout mice (IL-10−/−, n = 10) and wild-type mice (IL-10+/+, n = 10) were exposed to the following test gases: hyperoxic hypercapnia 7% CO2-93% O2, normoxic hypercapnia 7% CO2-21% O2, hypoxic hypercapnia 7% CO2-10% O2, and hypoxic normocapnia 3% CO2-10% O2. The ventilatory function was assessed using whole body plethysmography. Recombinant mouse IL-10 (rIL-10; 10 μg/kg) was administered intraperitoneally to wild-type mice ( n = 10) 30 min before the onset of gas challenge. IL-10 was administered in neonatal medullary slices (10–30 ng/ml, n = 8). We found that IL-10−/−mice exhibited consistently increased frequency and reduced tidal volume compared with IL-10+/+mice during room air breathing and in all test gases (by 23.62 to 33.2%, P < 0.05 and −36.23 to −41.69%, P < 0.05, respectively). In all inspired gases, the minute ventilation of IL-10−/−mice was lower than IL-10+/+(by −15.67 to −22.74%, P < 0.05). The rapid shallow breathing index was higher in IL-10−/−mice compared with IL-10+/+mice in all inspired gases (by 50.25 to 57.5%, P < 0.05). The intraperitoneal injection of rIL-10 caused reduction of the respiratory rate and augmentation of the tidal volume in room air and also in all inspired gases (by −12.22 to −29.53 and 32.18 to 45.11%, P < 0.05, respectively). IL-10 administration in neonatal rat ( n = 8) in vitro rhythmically active medullary slice preparations did not affect either rhythmicity or peak amplitude of hypoglossal nerve discharge. In conclusion, IL-10 may induce a slower and deeper pattern of breathing.

Nerve Injury Induces a Tonic Bilateral μ-Opioid Receptor–mediated Inhibitory Effect on Mechanical Allodynia in Mice

2004 ◽  
Vol 100 (4) ◽  
pp. 912-921 ◽  
Author(s):  
Heikki Mansikka ◽  
Chengshui Zhao ◽  
Rishi N. Sheth ◽  
Ichiro Sora ◽  
George Uhl ◽  
...  
Keyword(s):  
Nerve Injury ◽  
Opioid Receptor ◽  
Mechanical Allodynia ◽  
Mu Opioid Receptor ◽  
Spinal Nerve ◽  
Mechanical Stimuli ◽  
Wild Type ◽  
Mu Opioid Receptors ◽  
Kappa Opioid ◽  
Mu Opioid

Background Mice lacking the mu-opioid receptor gene have been used to characterize the role of mu-opioid receptors in nociception and the analgesic actions of opioid agonists. In this study, the authors determined the role of mu-opioid receptors in neuropathic pain behaviors and the effectiveness of mu- and kappa-opioid receptor agonists on this behavior in mice. Methods The authors studied the behavioral responses of mu-opioid receptor knockout and wild-type mice to thermal and mechanical stimuli before and after neuropathic pain induced by unilateral ligation and section of the L5 spinal nerve. Response to mechanical stimuli was evaluated by determining the frequency of hind paw withdrawal to repetitive stimulation using a series of von Frey monofilaments. Thermal hyperalgesia was assessed by determining the paw withdrawal latencies to radiant heat and frequency of hind paw withdrawal to cooling stimuli. The effects of systemic morphine, the kappa-opioid agonist U50488H, and naloxone on responses to mechanical and thermal stimuli were also studied in spinal nerve-injured mice. Results After spinal nerve injury, wild-type mice developed increased responsiveness to mechanical, heat, and cooling stimuli ipsilateral to nerve injury. mu-Opioid receptor knockout mice not only had more prominent mechanical allodynia in the nerve-injured paw, but also expressed contralateral allodynia to mechanical stimuli. Hyperalgesia to thermal stimuli was similar between mu-opioid knockout and wild-type animals. Morphine decreased mechanical allodynia dose dependently (3-30 mg/kg subcutaneous) in wild-type mice--an effect that was attenuated in the heterozygous mice and absent in the homozygous mu-opioid knockout mice. The kappa-opioid agonist U50488H (3-10 mg/kg subcutaneous) attenuated mechanical allodynia in wild-type, heterozygous, and homozygous mu-opioid mice. Naloxone in wild-type mice resulted in enhanced ipsilateral and contralateral allodynia to mechanical stimuli that resembled the pain behavior observed in mu-opioid receptor knockout mice. Conclusions The authors' observations indicate that (1) unilateral nerve injury induces a bilateral tonic activation of endogenous mu-opioid receptor-mediated inhibition that attenuates mechanical allodynia but not thermal hyperalgesia, (2) both mu- and kappa-opioid agonists attenuate neuropathic pain in mice, and (3) the antihyperalgesic actions of morphine are mediated primarily via mu-opioid receptors.

scholarly journals OPRM1 A118G and serum β-endorphin interact with sex and digit ratio (2D:4D) to influence risk and course of alcohol dependence

2017 ◽  
Author(s):  
Jordan Bruno Gegenhuber ◽  
Christian Weinland ◽  
Johannes Kornhuber ◽  
Christiane Mühle ◽  
Bernd Lenz
Keyword(s):  
Alcohol Dependence ◽  
Opioid Receptor ◽  
Sex Hormones ◽  
Receptor Gene ◽  
Drinking Behavior ◽  
Mu Opioid Receptor ◽  
Sex Hormone ◽  
Opioid System ◽  
Endogenous Opioid ◽  
Mu Opioid

AbstractActivation of mesolimbic mu-opioid receptor by its endogenous ligand, β-endorphin, mediates part of the rewarding effects of alcohol, yet there is controversial evidence surrounding the relationship between the functional mu-opioid receptor gene (OPRM1) A118G single nucleotide polymorphism and alcohol dependence risk. Some preclinical evidence suggests that sex and sex hormone-dependent prenatal brain organization may interact with the opioid system to influence alcohol drinking behavior. We genotyped 200 alcohol-dependent patients and 240 healthy individuals for the A118G variant and measured serum β-endorphin level at recruitment and during acute withdrawal. We then evaluated the association between these factors and alcohol dependence risk and outcome in the context of both sex and second-to-fourth digit length ratio (2D:4D) – a biomarker of prenatal sex hormone load. For the first time, the AA genotype was found to be associated with elevated alcohol-related hospital readmission risk, more readmissions, and fewer days until first readmission in male but not female patients. Upon accounting for 2D:4D, the G-allele predicted alcohol dependence and more readmissions (1 vs ≥2) in males, suggesting prenatal sex hormones interact with OPRM1 to influence addiction pathology. Withdrawal β-endorphin level also correlated negatively with withdrawal severity in females but not in males, indicating β-endorphin might protect against withdrawal-induced stress in a sex-specific manner. Organizational effects of sex hormones may prime individuals for alcohol dependence by inducing permanent changes to the endogenous opioid system.

Communication: Photoinduced Carbon Dioxide Binding with Surface-Functionalized Silicon Quantum Dots

2018 ◽  
Author(s):  
Oscar A. Douglas-Gallardo ◽  
Cristián Gabriel Sánchez ◽  
Esteban Vöhringer-Martinez
Keyword(s):  
Carbon Dioxide ◽  
Quantum Dots ◽  
Atmospheric Carbon Dioxide ◽  
Density Functional ◽  
Tight Binding ◽  
Carbon Dioxide Concentration ◽  
Research Area ◽  
Silicon Quantum Dots ◽  
Dependent Model ◽  
Photoinduced Charge

<div> <div> <div> <p>Nowadays, the search of efficient methods able to reduce the high atmospheric carbon dioxide concentration has turned into a very dynamic research area. Several environmental problems have been closely associated with the high atmospheric level of this greenhouse gas. Here, a novel system based on the use of surface-functionalized silicon quantum dots (sf -SiQDs) is theoretically proposed as a versatile device to bind carbon dioxide. Within this approach, carbon dioxide trapping is modulated by a photoinduced charge redistribution between the capping molecule and the silicon quantum dots (SiQDs). Chemical and electronic properties of the proposed SiQDs have been studied with Density Functional Theory (DFT) and Density Functional Tight-Binding (DFTB) approach along with a Time-Dependent model based on the DFTB (TD-DFTB) framework. To the best of our knowledge, this is the first report that proposes and explores the potential application of a versatile and friendly device based on the use of sf -SiQDs for photochemically activated carbon dioxide fixation. </p> </div> </div> </div>

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