We studied the activation of β2-adrenergic receptor（β2AR） by norepinephrine, epinephrine and isoprote- renol using docking and molecular dynamics（MD） simulation. The simulation was done on the assumption that β...We studied the activation of β2-adrenergic receptor（β2AR） by norepinephrine, epinephrine and isoprote- renol using docking and molecular dynamics（MD） simulation. The simulation was done on the assumption that β2AR was surrounded with explicit water and infinite lipid bilayer membrane at body temperature. So the result should be close to that under the physiological conditions. We calculated the structure of binding sites in β2AR for the three ac- tivators. We also simulated the change of the conformation ofβ2AR in the transmembrane regions（TMs）, in the mo- lecular switches, and in the conserved DRY（Aspartic acid, Arginine and Tyrosine） motif. This study provides detailed information concerning the structure ofβ2AR during activation process.展开更多
Primary lung graft dysfunction could significantly attribute to ischemia-reperfusion lung injury(IRLI)during transplantation surgery.β2-adrenergic agonists were one of the bronchodilators that had been well-establish...Primary lung graft dysfunction could significantly attribute to ischemia-reperfusion lung injury(IRLI)during transplantation surgery.β2-adrenergic agonists were one of the bronchodilators that had been well-established in the management of asthma and chronic obstructive pulmonary disease(COPD)with anti-inflammatory potency.By applying the model of isolated rat lung,we evaluated the efficacy of short-actingβ2-agonist inhalation to ameliorate ischemia-reperfusion damage.The experiment protocol was 180 min of global ischemia and then reperfusion for 60 min.In theβ2-agonist inhalation group,aerosolized albuterol was administrated prior ischemia procedure.Increased weight ratios of wet to dry lung and microvascular permeability were characterized in the IRLI group.In contrast,pre-inhaledβ2-agonist significantly mitigated the severity of pulmonary edema.Bronchoalveolar lavage from theβ2-agonist group presented decreased leukocyte counts and cytokines production,including interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and macrophage inflammatory protein 2(MIP-2).Devastating oxidative stress was widely recognized during the ischemia-reperfusion process,whileβ2-agonist pretreatment revealed subsided H2O2,myeloperoxidase(MPO),and the cleavage of caspase-3.Western blotting from lung homogenates identified the blockade of NF-κB and MAPK activation in theβ2-agonist inhalation group.Currently,there was no specific pharmacotherapy in IRLI management.Our results elucidated the protective effect ofβ2-agonist bronchodilator against ischemia-reperfusion induced oxidative stress,inflammation reaction,and pulmonary edema.展开更多
Lucemyra? (lofexidine hydrochloride) has recently been approved by the US FDA for the mitigation of withdrawal symptoms to facilitate abrupt discontinuation of opioids in adults. Lofexidine is an alpha-2 adrenoceptor ...Lucemyra? (lofexidine hydrochloride) has recently been approved by the US FDA for the mitigation of withdrawal symptoms to facilitate abrupt discontinuation of opioids in adults. Lofexidine is an alpha-2 adrenoceptor agonist. However, the clinical attributes of lofexidine differ in advantageous ways from the classical alpha-2 adrenoceptor agonist clonidine. In the present study, we measured the receptor binding profile of lofexidine and clonidine in an effort to gain an insight into the clinical difference(s).展开更多
Aim:In this review,it will mainly focus on clarifying the pharmacology of dexmedetomidine and discussing the past,present and future clinical applications of dexmedetomidine as an adjunct in anesthesia.Method:We have ...Aim:In this review,it will mainly focus on clarifying the pharmacology of dexmedetomidine and discussing the past,present and future clinical applications of dexmedetomidine as an adjunct in anesthesia.Method:We have searched and reviewed the articles about the use of dexmedetomidine in clinical anesthesia,intensive care unit(ICU),painless gastroenteroscopy and painless labor over the past two decades.Recent findings:Dexmedetomidine,a highly selective agonist of alpha2-adrenergic receptors(alpha2-AR),was primarily approved by the U.S.Food and Drug Administration(FDA)for sedation in ICU due to its pharmacological characteristics with sedative,analgesic and sympatholytic effects.These properties make up the limitations of anesthetics,and it produces a“dexmedetomidine assisted”anesthesia mode as an adjuvant combining with other anesthesia methods,which are all termed as“DEX+”.These new methods can reduce the anesthetics requirement but prolong the action period and alleviate the adverse reactions of anesthetics,thus improving the anesthesia more effectively and safely.Summary:Dexmedetomidine possesses the unique properties exerting synergistic effects and alleviating the side effects as an adjuvant in anesthesia through different administration routes.It is beneficial for the patients’long-term outcome and will be bound to be the leading innovator of anesthesia in future.展开更多
基金Supported by the Young and Middle-Aged Scientists Research Awards Foundation of Shangdong Province,China(No.BS2011SW002)the Research Foundation for Advanced Talents of Ludong University,China(No.LY2011017)
文摘We studied the activation of β2-adrenergic receptor（β2AR） by norepinephrine, epinephrine and isoprote- renol using docking and molecular dynamics（MD） simulation. The simulation was done on the assumption that β2AR was surrounded with explicit water and infinite lipid bilayer membrane at body temperature. So the result should be close to that under the physiological conditions. We calculated the structure of binding sites in β2AR for the three ac- tivators. We also simulated the change of the conformation ofβ2AR in the transmembrane regions（TMs）, in the mo- lecular switches, and in the conserved DRY（Aspartic acid, Arginine and Tyrosine） motif. This study provides detailed information concerning the structure ofβ2AR during activation process.
基金the Tri-Service General Hospital,National Defesnse Medical Center in Taiwan(TSGH-C108-109).
文摘Primary lung graft dysfunction could significantly attribute to ischemia-reperfusion lung injury(IRLI)during transplantation surgery.β2-adrenergic agonists were one of the bronchodilators that had been well-established in the management of asthma and chronic obstructive pulmonary disease(COPD)with anti-inflammatory potency.By applying the model of isolated rat lung,we evaluated the efficacy of short-actingβ2-agonist inhalation to ameliorate ischemia-reperfusion damage.The experiment protocol was 180 min of global ischemia and then reperfusion for 60 min.In theβ2-agonist inhalation group,aerosolized albuterol was administrated prior ischemia procedure.Increased weight ratios of wet to dry lung and microvascular permeability were characterized in the IRLI group.In contrast,pre-inhaledβ2-agonist significantly mitigated the severity of pulmonary edema.Bronchoalveolar lavage from theβ2-agonist group presented decreased leukocyte counts and cytokines production,including interleukin-1β(IL-1β),tumor necrosis factor-α(TNF-α),and macrophage inflammatory protein 2(MIP-2).Devastating oxidative stress was widely recognized during the ischemia-reperfusion process,whileβ2-agonist pretreatment revealed subsided H2O2,myeloperoxidase(MPO),and the cleavage of caspase-3.Western blotting from lung homogenates identified the blockade of NF-κB and MAPK activation in theβ2-agonist inhalation group.Currently,there was no specific pharmacotherapy in IRLI management.Our results elucidated the protective effect ofβ2-agonist bronchodilator against ischemia-reperfusion induced oxidative stress,inflammation reaction,and pulmonary edema.
文摘Lucemyra? (lofexidine hydrochloride) has recently been approved by the US FDA for the mitigation of withdrawal symptoms to facilitate abrupt discontinuation of opioids in adults. Lofexidine is an alpha-2 adrenoceptor agonist. However, the clinical attributes of lofexidine differ in advantageous ways from the classical alpha-2 adrenoceptor agonist clonidine. In the present study, we measured the receptor binding profile of lofexidine and clonidine in an effort to gain an insight into the clinical difference(s).
基金This study was supported by grants from the National Natural Science Foundation of China(No.81801175)the China Postdoctoral Science Foundation(No.2019M662179)+1 种基金the Anhui Province Postdoctoral Science Foundation(No.2019B324)the Fundamental Research Funds for the Central Universities(No.WK9110000044).
文摘Aim:In this review,it will mainly focus on clarifying the pharmacology of dexmedetomidine and discussing the past,present and future clinical applications of dexmedetomidine as an adjunct in anesthesia.Method:We have searched and reviewed the articles about the use of dexmedetomidine in clinical anesthesia,intensive care unit(ICU),painless gastroenteroscopy and painless labor over the past two decades.Recent findings:Dexmedetomidine,a highly selective agonist of alpha2-adrenergic receptors(alpha2-AR),was primarily approved by the U.S.Food and Drug Administration(FDA)for sedation in ICU due to its pharmacological characteristics with sedative,analgesic and sympatholytic effects.These properties make up the limitations of anesthetics,and it produces a“dexmedetomidine assisted”anesthesia mode as an adjuvant combining with other anesthesia methods,which are all termed as“DEX+”.These new methods can reduce the anesthetics requirement but prolong the action period and alleviate the adverse reactions of anesthetics,thus improving the anesthesia more effectively and safely.Summary:Dexmedetomidine possesses the unique properties exerting synergistic effects and alleviating the side effects as an adjuvant in anesthesia through different administration routes.It is beneficial for the patients’long-term outcome and will be bound to be the leading innovator of anesthesia in future.
