Temporomandibular joint osteoarthritis (TMJ-OA) is a common disease often accompanied by pain, seriously affecting physical and mental health of patients. Abnormal innervation at the osteochondral junction has been considered as a predominant origin of arthralgia, while the specific mechanism mediating pain remains unclear. To investigate the underlying mechanism of TMJ-OA pain, an abnormal joint loading model was used to induce TMJ-OA pain. We found that during the development of TMJ-OA, the increased innervation of sympathetic nerve of subchondral bone precedes that of sensory nerves. Furthermore, these two types of nerves are spatially closely associated. Additionally, it was discovered that activation of sympathetic neural signals promotes osteoarthritic pain in mice, whereas blocking these signals effectively alleviates pain. In vitro experiments also confirmed that norepinephrine released by sympathetic neurons promotes the activation and axonal growth of sensory neurons. Moreover, we also discovered that through releasing norepinephrine, regional sympathetic nerves of subchondral bone were found to regulate growth and activation of local sensory nerves synergistically with other pain regulators. This study identified the role of regional sympathetic nerves in mediating pain in TMJ-OA. It sheds light on a new mechanism of abnormal innervation at the osteochondral junction and the regional crosstalk between peripheral nerves, providing a potential target for treating TMJ-OA pain.
Animals ; Osteoarthritis/physiopathology* ; Mice ; Sympathetic Nervous System/physiopathology* ; Temporomandibular Joint Disorders/physiopathology* ; Arthralgia ; Sensory Receptor Cells ; Disease Models, Animal ; Norepinephrine ; Male ; Temporomandibular Joint/physiopathology* ; Pain Measurement

OBJECTIVE: To elucidate the predictive value of norepinephrine equivalence (NEE) score on the 28-day death risk in patients with sepsis and provide evidence for its application in the diagnosis and treatment of sepsis and septic shock. METHODS: A retrospective cohort study was conducted based on the data of patients with sepsis from Medical Information Mart for Intensive Care-IV 2.2 (MIMIC-IV 2.2). The patients who received vasoactive agents within 6 hours after the diagnosis of sepsis or septic shock were enrolled, and they were divided into survival and non-survival groups based on their 28-day outcomes. The baseline characteristics, vital signs, and treatment data were collected. Multivariate Cox regression analysis was performed to identify factors influencing the 28-day death risk. Receiver operator characteristic curve (ROC curve) was drawn to analyze the predictive value of various parameters on the 28-day death risk of septic patients. Kaplan-Meier survival curve was used to evaluate cumulative survival rate in patients classified by different quantitative parameters based on the cut-off values obtained from ROC curve analysis. RESULTS: A total of 7 744 patients who met the Sepsis-3 diagnostic criteria and received vasopressor treatment within 6 hours post-diagnosis were enrolled, of which 5 997 cases survived and 1 747 died, with the 28-day mortality of 22.6%. Significant differences were observed between the two groups regarding age, gender, height, body weight, race, type of intensive care unit (ICU), acute physiology and chronic health evaluation II (APACHE II) score, sequential organ failure assessment (SOFA) score, Charlson comorbidity index (CCI) score, underlying comorbidities, and vital signs. Compared with the survival group, the non-survival group had poorer blood routine, liver and kidney function, coagulation function, blood gas analysis and other indicators. Multivariate Cox regression analysis revealed that age > 65 years old [hazard ratio (HR) = 0.892, 95% confidence interval (95%CI) was 0.801-0.994, P = 0.039] and male (HR = 0.735, 95%CI was 0.669-0.808, P < 0.001) were protective factors for 28-day death in patients with sepsis, and NEE score (HR = 1.040, 95%CI was 1.021-1.060, P < 0.001), shock index (HR = 1.840, 95%CI was 1.675-2.022, P < 0.001), APACHE II score (HR = 1.076, 95%CI was 1.069-1.083, P < 0.001), SOFA score (HR = 1.035, 95%CI was 1.015-1.056, P < 0.001), and CCI score (HR = 1.135, 95%CI was 1.115-1.155, P < 0.001) were independent risk factors for 28-day death in septic patients. ROC curve analysis showed that the area under the ROC curve (AUC) of NEE score for predicting the 28-day death risk of septic patients was 0.743 (95%CI was 0.730-0.756), which was comparable to the predictive value of APACHE II score (AUC = 0.742, 95%CI was 0.729-0.755) and ratio of mean arterial pressure (MAP)/NEE score (MAP/NEE; AUC = 0.738, 95%CI was 0.725-0.751, both P > 0.05), and better than SOFA score (AUC = 0.609, 95%CI was 0.594-0.624), CCI score (AUC = 0.658, 95%CI was 0.644-0.673), shock index (AUC = 0.613, 95%CI was 0.597-0.629) and ratio of diastolic blood pressure (DBP)/NEE score (DBP/NEE; AUC = 0.735, 95%CI was 0.721-0.748, all P < 0.05). According to the cut-off values of APACHE II and NEE scores obtained from ROC curve analysis, the patients were stratified for Kaplan-Meier survival curve analysis, and the results showed that the 28-day cumulative survival rate in the septic patients with an APACHE II score ≤ 22.5 was significantly higher than that in those with an APACHE II > 22.5 (Log-Rank test: χ² = 848.600, P < 0.001), and the 28-day cumulative survival rate in the septic patients with an NEE score ≤0.120 was significantly higher than that in those with an NEE score > 0.120 (Log-Rank test: χ² = 832.449, P < 0.001). CONCLUSIONS NEE score is an independent risk factor for 28-day death in septic patients who received vasoactive treatment within 6 hours of diagnosis and possesses significant predictive value. It can be used for severity stratification in sepsis management.
Humans ; Retrospective Studies ; Sepsis/diagnosis* ; Male ; Female ; Norepinephrine/therapeutic use* ; Middle Aged ; Aged ; Prognosis ; Predictive Value of Tests ; Shock, Septic/mortality* ; Adult ; ROC Curve ; Risk Factors ; Survival Rate ; Aged, 80 and over

Traumatic brain injury (TBI), as a significant central nervous system damage disease with high frequency in the world, leads to a huge number of patients with impaired health and lower quality of life every year. Lung injury is a common and dangerous consequence, which dramatically raises the mortality of patients. Discovering the pathophysiology of lung injury after TBI and discovering viable therapeutic targets has become an important need for clinical diagnosis and therapy. Neurotransmitters, as the fundamental chemical agents of the nervous system for signal transmission, not only govern neuronal activity and apoptosis in TBI but also significantly influence the pathophysiological mechanisms of lung injury subsequent to TBI. The imbalance is intricately linked to the onset and progression of lung damage. This paper systematically reviews the clinical characteristics and predominant pathogenesis of lung injury following TBI, emphasizing the role of key neurotransmitters, including glutamate (Glu), γ-aminobutyric acid (GABA), norepinephrine (NE), dopamine (DA), and acetylcholine (ACh), in lung injury post-TBI. It examines their influence on inflammatory response, vascular permeability, and pulmonary circulation function. Additionally, the paper evaluates the research advancements and potential applications of targeted therapeutic strategies for various neurotransmitter systems, such as receptor antagonists, transporter inhibitors, and neurotransmitter analogues. This research aims to offer a theoretical framework for clarifying the neural regulatory mechanisms of lung injury following TBI and to establish a basis for the development of novel therapeutic strategies and enhancement of the prognosis of the patients.
Humans ; Brain Injuries, Traumatic/metabolism* ; Neurotransmitter Agents/metabolism* ; Lung Injury/metabolism* ; gamma-Aminobutyric Acid/metabolism* ; Glutamic Acid/metabolism* ; Norepinephrine/metabolism* ; Dopamine/metabolism* ; Acetylcholine/metabolism*

Humans ; Norepinephrine ; Bacterial Infections/drug therapy* ; Immunity, Innate

OBJECTIVE: To investigate the effects of umbilical moxibustion therapy on phobic behavior and the contents of norepinephrine (NE), dopamine (DA) and 5-hydroxytryptamine (5-HT) in different brain regions of the stress-model rats and explore the potential mechanism of umbilical moxibustion on phobic behavior. METHODS: Among 50 Wistar male rats, 45 rates were selected and randomly divided into a control group, a model group and an umbilical moxibustion group, 15 rats in each one; and the rest 5 rats were used for preparing the model of electric shock. The bystander electroshock method was adopted to prepare phobic stress model in the model group and the umbilical moxibustion group. After modeling, the intervention with umbilical moxibustion started in the umbilical moxibustion group, in which, the ginger-isolated moxibustion was applied at "Shenque" (CV 8), once daily, 2 cones for 20 min each time, for consecutively 21 days. After modeling and intervention completed, the rats in each group were subjected to the open field test to evaluate the state of fear. After intervention, the Morris water maze test and fear conditioning test were performed to evaluate the changes in learning and memory ability and the state of fear. Using high performance liquid chromatography (HPLC), the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were determined. RESULTS: Compared with the control group, the horizontal and vertical activity scores were lower (P<0.01), the number of stool particles was increased (P<0.01), the escape latency was prolonged (P<0.01), the times of target quadrant were reduced (P<0.01), and the freezing time was prolonged (P<0.05) in the rats of the model group. The horizontal and vertical activity scores were increased (P<0.05), the number of stool particles was reduced (P<0.05), the escape latency was shortened (P<0.05, P<0.01), the times of target quadrant were increased (P<0.05), and the freezing time was shortened (P<0.05) in the rats of the umbilical moxibustion group when compared with the model group. The trend search strategy was adopted in the control group and the umbilical moxibustion group, while the random search strategy was used in rats of the model group. Compared with the control group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were reduced (P<0.01) in the model group. In the umbilical moxibustion group, the contents of NE, DA and 5-HT in the hippocampus, prefrontal cortex and hypothalamus were increased (P<0.05, P<0.01) when compared with the model group. CONCLUSION Umbilical moxibustion can effectively relieve the state of fear and learning and memory impairment of phobic stress model rats, which may be related to the up-regulation of contents of brain neurotransmitters, i.e. NE, DA, and 5-HT.
Rats ; Male ; Animals ; Moxibustion ; Rats, Sprague-Dawley ; Rats, Wistar ; Serotonin ; Hippocampus ; Dopamine ; Norepinephrine ; Neurotransmitter Agents

OBJECTIVE: To evaluate the effect of transcutaneous acupoint electrical stimulation (TEAS) at Neiguan (PC 6) on general anesthesia under preserving spontaneous breathing in thoracoscopic lobectomy. METHODS: A total of 66 patients of primary lung cancer undergoing thoracoscopic lobectomy were divided to an observation group (33 cases, 1 case discontinued) and a control group (33 cases). In the observation group, TEAS at Neiguan (PC 6) was used 30 min before anesthesia induction till the end of surgery. The surgery time, maximum value of partial pressure of end-tidal carbon dioxide (P_ETCO₂) and minimum value of oxygen saturation (SpO₂) of the two groups were recorded. The dosage of propofol, sufentanil, remifentanil and dexmedetomidine were analyzed. Separately, before induction (T₀), at the start of surgery (T₁), thoracic exploration (T₂) and lobectomy (T₃), as well as 30 min (T₄) and 60 min (T₅) after lobectomy, the mean arterial pressure (MAP), heart rate (HR), respiratory rate (RR), serum cortisol (Cor) and norepinephrine (NE) were measured. The time of post anesthesia care unit (PACU) stay, ambulation, flatus, chest drainage and the incidence of nausea and vomiting were compared between the two groups. RESULTS: The maximum value of P_ETCO₂, the dosage of propofol and remifentanil in the observation group were lower than those in the control group (P < 0.05, P < 0.01), the minimum value of SpO₂ in the observation group was higher than that of the control group (P < 0.01). At T₁-T₅, the MAP, HR, serum Cor and NE levels in the observation group were all lower than those in the control group (P < 0.05). The ambulation time, the time for the flatus, chest drainage time, and the incidence of nausea and vomiting in the observation group were all lower than those in the control group (P<0.001, P < 0.01). CONCLUSION For the general anesthesia under preserving spontaneous breathing in thoracoscopic surgery, TEAS at Neiguan (PC 6) relieves stress response, reduces opioids dosage and promotes postoperative recovery.
Humans ; Acupuncture Points ; Carbon Dioxide ; Flatulence ; Propofol ; Remifentanil ; Anesthesia, General ; Nausea ; Norepinephrine ; Electric Stimulation

Objective To determine the optimal dosage and intervention duration of reserpine to establish a rat model of hypotension.Methods According to the body weight and systolic blood pressure (SBP),60 male Wistar rats were assigned to six groups (n=10),including a control group and five observation groups with different doses.The control group was administrated with 10 ml/kg 0.5% sodium carboxymethyl cellulose solution,and the observation groups with 0.016,0.032,0.064,0.128,and 0.160 mg/kg reserpine suspensions,respectively.All the groups were administrated by gavage twice a day,and the body weights of rats were monitored daily.SBP and heart rate (HR) were measured before modeling and 1-6 weeks after administration.After 6 weeks of administration,the blood samples of inner canthus were collected.The levels of lactate dehydrogenase (LDH),creatine kinase MB isoenzyme (CK-MB),alanine aminotransferase,aspartate aminotransferase (AST),serum creatinine,and blood urea nitrogen (BUN) were measured by an autoanalyzer.Three rats in each group were randomly selected for observation of the changes in SBP after drug withdrawal and the rest rats were sacrificed for measurement of the levels of norepinephrine and dopamine in the brain.Results Compared with the control group,different doses of reserpine lowered the SBP of rats (F=28.492,P<0.001).The decline in SBP increased in a concentration-dependent manner.SBP reached the lowest value after 1 week,rose slightly later,and was stable after 3 weeks of administration.There was no significant difference in SBP between 0.016 mg/kg reserpine group and the control group after the 5th week (P>0.05).The SBP levels of rats in 0.032,0.064,0.128,and 0.160 mg/kg reserpine groups showed no significant difference between each other (P=0.204) and were lower than that in the control group (all P<0.001).One week after drug withdrawal,the SBP of rats in the observation groups rose to the baseline level and remained stable.HR showed similar changes among groups,first increasing and then decreasing.There was no significant difference in HR among different groups at the same time point (F=0.922,P=0.475).Compared with the control group,reserpine of different doses reduced the norepinephrine content in the hippocampus (all P<0.001),and 0.128 mg/kg (P=0.045) and 0.160 mg/kg (P=0.042) reserpine lowered the dopamine level in the striatum,which showed no significant differences between different reserpine groups(P=0.343,P=0.301).The levels of LDH,CK-MB,and BUN in the serum increased with the increase in reserpine concentration,and the levels of LDH (P=0.001),CK-MB (P=0.020),AST (P=0.007),and BUN (P=0.001) in the 0.160 mg/kg reserpine group were significantly different from those in the control group.Conclusions The rat model of hypotension can be induced by gavage with reserpine.The gavage with reserpine at a dose of 0.032 mg/kg,twice a day for three consecutive weeks is the optimal scheme for the modeling.After the model establishment,continuous administration is essential to maintain the hypotension.
Male ; Rats ; Animals ; Reserpine ; Dopamine ; Rats, Wistar ; Hypotension/chemically induced* ; Norepinephrine

OBJECTIVE: To investigate the correlation between early-stage blood pressure indexes and prognosis in sepsis patients. METHODS: A retrospective cohort study was conducted on the medical records of patients diagnosed with sepsis from 2001 to 2012 in the Medical Information Mart for Intensive Care-III (MIMIC-III) database. Patients were divided into survival group and death group according to the 28-day prognosis. General data of patients and heart rate (HR) and blood pressure at admission to ICU and within 24 hours after admission were collected. The blood pressure indexes including the maximum, median and mean value of systolic index, diastolic index and mean arterial pressure (MAP) index were calculated. The data were randomly divided into training set and validation set (4 : 1). Univariate Logistic regression analysis was used to screen covariates, and multivariate Logistic stepwise regression models were further developed. Model 1 (including HR, blood pressure, and blood pressure index related variables with P < 0.1 and other variables with P < 0.05) and Model 2 (including HR, blood pressure, and blood pressure index related variables with P < 0.1) were developed respectively. The receiver operator characteristic curve (ROC curve), precision recall curve (PRC) and decision curve analysis (DCA) curve were used to evaluate the quality of the two models, and the influencing factors of the prognosis of sepsis patients were analyzed. Finally, nomogram model was developed according to the better model and effectiveness of it was evaluated. RESULTS: A total of 11 559 sepsis patients were included in the study, with 10 012 patients in the survival group and 1 547 patients in the death group. There were significant differences in age, survival time, Elixhauser comorbidity score and other 46 variables between the two groups (all P < 0.05). Thirty-seven variables were preliminarily screened by univariate Logistic regression analysis. After multivariate Logistic stepwise regression model screening, among the indicators related to HR, blood pressure and blood pressure index, the HR at admission to ICU [odds ratio (OR) = 0.992, 95% confidence interval (95%CI) was 0.988-0.997] and the maximum HR (OR = 1.006, 95%CI was 1.001-1.011), maximum MAP index (OR = 1.620, 95%CI was 1.244-2.126), mean diastolic index (OR = 0.283, 95%CI was 0.091-0.856), median systolic index (OR = 2.149, 95%CI was 0.805-4.461), median diastolic index (OR = 3.986, 95%CI was 1.376-11.758) were selected (all P < 0.1). There were 14 other variables with P < 0.05, including age, Elixhauser comorbidity score, continuous renal replacement therapy (CRRT), use of ventilator, sedation and analgesia, norepinephrine, norepinephrine, highest serum creatinine (SCr), maximum blood urea nitrogen (BUN), highest prothrombin time (PT), highest activated partial thromboplastin time (APTT), lowest platelet count (PLT), highest white blood cell count (WBC), minimum hemoglobin (Hb). The ROC curve showed that the area under the curve (AUC) of Model 1 and Model 2 were 0.769 and 0.637, respectively, indicating that model 1 had higher prediction accuracy. The PRC curve showed that the AUC of Model 1 and Model 2 were 0.381 and 0.240, respectively, indicating that Model 1 had a better effect. The DCA curve showed that when the threshold was 0-0.8 (the probability of death was 0-80%), the net benefit rate of Model 1 was higher than that of Model 2. The calibration curve showed that the prediction effect of the nomogram model developed according to Model 1 was in good agreement with the actual outcome. The Bootstrap verification results showed that the nomogram model was consistent with the above results and had good prediction effects. CONCLUSIONS The nomogram model constructed has good prediction effects on the 28-day prognosis in sepsis patients, and the blood pressure indexes are important predictors in the model.
Humans ; Cohort Studies ; Retrospective Studies ; Blood Pressure ; Intensive Care Units ; ROC Curve ; Sepsis/diagnosis* ; Prognosis ; Critical Care ; Norepinephrine

Objective: To summarize and analyze the clinical effect of fecal microbiota transplantation (FMT) combined with nutritional support and psychotherapy in patients with "Tetralogy of Tongji" (comprising chronic gastrointestinal dysfunction, mental and psychological disorders, malnutrition, and endocrine disorders). Methods: A longitudinal study was conducted. The inclusion criteria were as follows: (1) patients were under 70 years of age; (2) patients exhibited chronic gastrointestinal dysfunction (in accordance with the Rome IV diagnostic criteria for irritable bowel syndrome ie. chronic functional constipation, diarrhea, abdominal pain and abdominal distention) with onset occurring more than one year previously; (3) patients exhibited malnutrition (body mass index ≤ 18.5 kg/m²); (4) patients exhibited depression, anxiety, or state as diagnosed by a psychologist using the Hamilton anxiety rating scale (HAMA) and the Hamilton depression scale (HAMD); (5) patients were women of childbearing age with amenorrhea or menstrual disorder with a duration ≥6 months. Patients were excluded if they exhibited gastrointestinal bleeding, short bowel syndrome, radiation-induced intestinal injury, intestinal obstruction or inflammatory bowel disease, recurrent/metastatic tumors, systemic infectious diseases, life-threatening systemic comorbidities, intorlerate to nasojejunal, percutaneous gastrostomy / jejunostomy or FMT. The clinical data of 43 patients at Shanghai Tenth People's Hospital exhibiting the "Tetralogy of Tongji" and who received microflora transplantation combined with nutritional support and psychotherapy from June 2017 to June 2021 was prospectively collected. There were 12 males and 31 females with a mean age of 35.2±16.7 years. All 43 patients had chronic gastrointestinal dysfunction. Of these, 24 patients had depression and 19 had anxiety. There were 26 women of reproductive age, including 13 cases of menstrual disorder and 9 cases of amenorrhea. The treatment intervention was a combination of FMT (microflora solution or microflora capsule), nutritional support (enteral nutrition) and psychological intervention. The following were assessed before treatment and 1, 3, 6 months after treatment: (1) gastrointestinal function was assessed using the gastrointestinal symptoms rating scale (GSRS), where a higher score is indicative of more serious gastrointestinal symptoms, and the gastrointestinal quality of life index (GIQLI), where a higher score is indicative of higher quality of life; (2) psychological status was assessed using HAMA and HAMD scores, where a lower score is indicative of reduced severity of anxiety or depression symptoms, respectively; (3) nutritional status was assessed by measurements of total blood protein, albumin, fibrinogen and prealbumin, as well as measurements of body mass and body mass index (BMI); (4) neuroendocrine function was assessed by measurement of blood levels of cortisol, dopamine and noradrenaline, as well as menstruation in women of reproductive age. Results: The follow-up rates at 1, 3 and 6 months after treatment were 90.7% (39/43), 72.1% (31/43) and 55.8% (24/43), respectively. The total effective rate for chronic gastrointestinal dysfunction was 81.4% (35/43), of which the average GSRS score decreased from 29.35±3.56 before treatment to 18.25±2.56 in the sixth month (P<0.001). The average GIQLI score increased from 56.23±10.34 before treatment to 91.04±20.39 in the sixth month (P<0.001). All patients had malnutrition before treatment. After 6 months, their body weight had increased from 40.61±8.88 kg to 50.45±6.23 kg (P<0.001), and BMI had increased from 15.17±1.87 kg/m² to 19.58±1.42 kg/m² (P<0.001). The average total protein level was 60.99± 5.99 g/L before treatment. After 6 months, this had increased to 64.21±4.23 g/L (F=2.715, P=0.022). The average prealbumin level increased from 150.14±56.04 mg/L before treatment to 258.17±86.94 mg/L after 6 months (F=15.124, P<0.001). In this study, 24 patients with depression/depressed state were included. After treatment, the average HAMD score in these patients decreased from 22.79±6.63 before treatment to 9.92±7.24 after 6 months (P<0.001). There were 19 patients with anxiety disorder/anxiety state. After treatment, the average HAMA score in these patients decreased from 17.15±4.34 before treatment to 7.73±4.10 after 6 months (P<0.001). Observing the endocrine efficacy of 26 women of childbearing age, it was found that the effective rate of this treatment on endocrine regulation was 69.2% (18/26). Although there was no significant change in blood cortisol levels after 6 months, average blood dopamine levels decreased from 32.91±10.65 nmol/L before treatment to 13.02±5.58 nmol/L after 6 months (P<0.001). Average blood norepinephrine levels decreased from 49.75±15.23 ng/L before treatment to 19.21±9.58 ng/L after 6 months (P<0.001). Conclusion: The strategy of FMT combined with nutritional support and psychological intervention is effective in improving the symptoms of the "Tetralogy of Tongji".
Adolescent ; Adult ; Amenorrhea ; China ; Constipation ; Dopamine ; Fecal Microbiota Transplantation ; Female ; Fibrinogen ; Gastrointestinal Diseases ; Humans ; Hydrocortisone ; Infant ; Longitudinal Studies ; Male ; Malnutrition ; Middle Aged ; Norepinephrine ; Nutritional Support ; Prealbumin ; Psychosocial Intervention ; Quality of Life ; Treatment Outcome ; Young Adult

A large number of β-adrenergic receptor (β-AR) agonists and antagonists are widely used in the treatment of cardiovascular diseases and other diseases. Nonetheless, it remains unclear whether these commonly used β-AR drugs can activate downstream β- arrestin-biased signaling pathways. The objective of this study was to investigate β-arrestin2 recruitment effects of β-AR agonists and antagonists that were commonly used in clinical practice. We used TANGO (transcriptional activation following arrestin translocation) assay to detect the β-arrestin2 recruitment by β-AR ligands in HEK293 cell line (HTLA cells) stably transfected with tetracycline transactivator protein (tTA) dependent luciferase reporter and β-arrestin2-TEV fusion gene. Upon activation of β-AR by a β-AR ligand, β-arrestin2 was recruited to the C terminus of the receptor, followed by cleavage of the G protein-coupled receptors (GPCRs) fusion protein at the TEV protease-cleavage site. The cleavage resulted in the release of tTA, which, after being transported to the nucleus, activated transcription of the luciferase reporter gene. The results showed that β-AR non-selective agonists epinephrine, noradrenaline and isoprenaline all promoted β-arrestin2 recruitment at β1-AR and β2-AR. β1-AR selective agonists dobutamine and denopamine both promoted β-arrestin2 recruitment at β1-AR. β2-AR selective agonists procaterol and salbutamol promoted β-arrestin2 recruitment at β2-AR. β-AR non-selective antagonists alprenolol and pindolol promoted β-arrestin2 recruitment at β1-AR. β1-AR selective antagonists celiprolol and bevantolol showed β-arrestin2 recruitment at β1-AR. β2-AR selective antagonists butoxamine showed β-arrestin2 recruitment at β1-AR. These results provide some clues for the potential action of β-AR drugs, and lay a foundation for the screening of β-arrestin-biased β-AR ligands.
Humans ; beta-Arrestin 2/metabolism* ; HEK293 Cells ; Adrenergic beta-Agonists/pharmacology* ; Isoproterenol/pharmacology* ; Receptors, Adrenergic, beta-2/metabolism* ; Norepinephrine/pharmacology*