Effects Of Terbutaline Research Articles

Clinical Analysis of Terbutaline and Budesonide Co-Treatment for Chronic Obstructive Pulmonary Disease

Objective: To analyze the clinical effect of terbutaline combined with budesonide in the treatment of chronic obstructive pulmonary disease. Methods: 500 cases of patients with chronic obstructive pulmonary disease admitted to the hospital from January 2022 to December 2023 were selected and divided into 250 cases in the control group and 250 cases in the observation group by randomization method, both groups received conventional symptomatic treatment, with budesonide added to the control group and terbutaline and budesonide to the observation group, and the lung function indexes, therapeutic effects and adverse drug reactions before and after treatment were compared. Results: After treatment, the level of all lung function indexes of patients in the observation group was higher than that of the control group, and the level of total effective rate of treatment was 96.40%, which was higher than that of the control group (P < 0.05), and the difference in the incidence rate of adverse reactions between the two groups was not strong (P > 0.05). Conclusion: In the clinical treatment of chronic obstructive pulmonary disease, the combined use of terbutaline and budesonide can positively improve lung function, with precise effects and few adverse reactions.

In vitro EVALUATION of THE EFFECTS of POTENTIAL GSK-3β INHIBITORS TERBUTALINE and ORCIPRENALINE

Lung cancer is a type of cancer that is mostly diagnosed at an advanced stage and has a short survival time despite standard chemotherapy and targeted therapies. Terbutaline and Orciprenaline are bronchodilator agent that are potent and selective β2 receptor agonists. The purpose of this study was to investigate by continuous monitoring to assay the effects of Terbutaline and Orciprenaline on human lung carcinoma cell line. Cells were treated 1, 10, 100, 200, 400 µM concentrations with Terbutaline/Orciprenaline. MTT assay and xCELLigence real-time cell analyzer were used to determine these compounds effect on cell viability. The cell index was monitored continuously by visualizing the impedance of the E-plate wells. Because of GSK3β roles in a diverse range of cellular processes like metabolism, cell proliferation, differentiation and survival and its key position at several signaling pathways, GSK3β inhibition was investigated of these molecules. It has been determined that Terbutaline and Orciprenaline inhibits GSK-3β.
 This is the first known study to demonstrate the effects of Terbutaline and Orciprenaline on A549 and the human bronchial epithelial cell line Beas-2b in real time. In this study, it was detected that Terbutaline and especially Orciprenaline may have potential therapeutic effects in lung carcinoma.

Noradrenaline Extravasation Management in the Absence of Phentolamine: A Case Series

Noradrenaline (norepinephrine) extravasation can lead to tissue ischemia due to its vasoconstrictive properties. Phentolamine is the preferred treatment but is often unavailable in many Malaysian healthcare facilities. Alternative treatments, such as topical glyceryl trinitrate (GTN) and terbutaline injections, have limited data supporting their use. This case series reports two instances of noradrenaline extravasation successfully managed with terbutaline injections and extemporaneously prepared topical GTN in an Emergency Department setting. These cases highlight the effectiveness of terbutaline and GTN as viable alternatives, providing valuable insights for emergency care in settings where phentolamine is not accessible.

The β2-adrenergic receptor agonist terbutaline upregulates T helper-17 cells in a protein kinase A-dependent manner

BackgroundT helper 17 (Th17) cells produce IL-17A cytokine and can exacerbate autoimmune diseases and asthma. The β2 adrenergic receptor is a g protein-coupled receptor that induces cAMP second messenger pathways. We tested the hypothesis that terbutaline, a β2-adrenergic receptor-specific agonist, promotes IL-17 secretion by memory Th17 cells in a cAMP and PKA-dependent manner. MethodsVenous peripheral blood mononuclear cells (PBMC) from healthy human participants were activated with anti-CD3 and anti-CD28 antibodies. Secreted IL-17A was measured by enzyme linked immunosorbent assay, intracellular IL-17A, and RORγ were measured using flow cytometry, and RORC by qPCR. Memory CD3+CD4+CD45RA-CD45RO+ T cells were obtained by immunomagnetic negative selection and activated with tri-antibody complex CD3/CD28/CD2. Secreted IL-17A, intracellular IL-17A, RORC were measured, and phosphorylated-serine133-CREB was measured by western blotting memory Th cells. ResultsTerbutaline increased IL-17A (p < 0.001), IL-17A+ cells (p < 0.05), and RORC in activated PBMC and memory Th cells. The PKA inhibitors H89 (p < 0.001) and Rp-cAMP (p < 0.01) abrogated the effects of terbutaline on IL-17A secretion in PBMC and memory T cells. Rolipram increased IL-17A (p < 0.01) to a similar extent as terbutaline. P-Ser133-CREB was increased by terbutaline (p < 0.05) in memory T cells. ConclusionTerbutaline augments memory Th17 cells in lymphocytes from healthy participants. This could exacerbate autoimmune diseases or asthma, in cases where Th17 cells are considered to be pro-inflammatory.

Combined uterorelaxant effect of magnesium sulfate and terbutaline: Studies on late pregnant rat uteri in vitro and in vivo.

Preterm delivery and its complications are among the biggest challenges and health risks in obstetrical practice. Several tocolytic agents are used in clinical practice, although the efficacy and side effect profiles of these drugs are not satisfying. The aim of this study was to investigate the uterus relaxant effect of the coadministration of β2 -mimetic terbutaline and magnesium sulfate (MgSO4 ) in an isolated organ bath and to perform in vivo smooth muscle electromyographic (SMEMG) studies in pregnant rats. In addition, we also investigated whether the tachycardia-inducing effect of terbutaline can be reduced by the presence of magnesium, due to the opposite heart rate modifying effects of the two agents. In the isolated organ bath studies, rhythmic contractions of 22-day- pregnant Sprague-Dawley rats were stimulated with KCl, and cumulative dose-response curves were constructed in the presence of MgSO4 or terbutaline. The uterus-relaxing effects of terbutaline were also investigated in the presence of MgSO4 in both normal buffer and Ca2+ -poor buffer. The in vivo SMEMG studies were carried out under anesthesia with the subcutaneous implantation of an electrode pair. The animals were treated with MgSO4 or terbutaline alone or in combination in a cumulative bolus injection. The implanted electrode pair also detected the heart rate. Both MgSO4 and terbutaline reduced uterine contractions in vitro and in vivo, furthermore, the administration of a small dose of MgSO4 significantly enhanced the relaxant effect of terbutaline, especially in the lower range. However, in Ca2+ -poor environment, MgSO4 was not able to increase the effect of terbutaline, indicating the role of MgSO4 as a Ca2+ channel blocker. In the cardiovascular studies, MgSO4 significantly decreased the tachycardia-inducing effect of terbutaline in late pregnant rats. The combined application of MgSO4 and terbutaline may have clinical significance in tocolysis, which must be confirmed in clinical trials. Furthermore, MgSO4 could substantially reduce the tachycardia-inducing side effect of terbutaline.

Terbutaline attenuates LPS-induced injury of pulmonary microvascular endothelial cells by cAMP/Epac signaling.

Acute lung injury (ALI), characterized by an acute onset of severe hypoxemia, is a common and devastating syndrome usually triggered by lipopolysaccharide (LPS) infection from bacteria. This study is intended to explore whether terbutaline can alleviate LPS-induced human pulmonary microvascular endothelial cell (HPMVEC) injury through cAMP/Epac signaling. LPS was utilized to induce ALI in HPMVECs, and after exposure of LPS-induced HPMVECs to terbutaline, the cellular functions including cell viability and apoptosis were measured by cell counting kit-8 and terminal deoxynucleotidyl transferase dUTP nick-end labeling. The protein expression related to cAMP/Epac signaling, apoptosis, and that of tight junction and inflammatory factors were evaluated at the same time. The effects of terbutaline on cellular functions were confirmed again after the addition of antagonists of cAMP and Epac, respectively. The levels of both cAMP and Epac reduced by LPS was concentration-dependently increased by terbutaline. The apoptosis and endothelial cell permeability damage of LPS-induced HPMVECs were enhanced after the addition of KT-5720 and ESI-09. The beneficial effects of terbutaline on alleviating the inflammation and apoptosis in HPMVECs injured by LPS are mediated by cAMP/Epac signaling, and this evidence would demonstrate the potential of terbutaline in the treatment of ALI.

Effect of Terbutaline Combined with Glucocorticoid in the Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Effect of Terbutaline Combined with Glucocorticoid in the Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease

Terbutaline, forskolin and cAMP reduce secretion of aqueous humour in the isolated bovine eye.

In order to elucidate involvement of cyclic AMP and intracellular Ca2+,[Ca2+]i, in the modulation of aqueous humour formation (AHF), we studied the effects of terbutaline, forskolin and 8-Br-cAMP in the isolated bovine eye. We also studied the interaction of cAMP on calcium signaling in cultured ciliary epithelial (CE) cells. Drug effects on AHF were measured by fluorescein dilution. Drug effects on [Ca2+]i were studied by the fura-2 fluorescence ratio technique. Terbutaline (100 nmol-100 M), forskolin (30 nM-100 M) or 8-Br-cAMP (100 nM- 10 μM), administered in the arterial perfusate produced significant reductions in AHF. The AH reducing effect of terbutaline was blocked by a selective inhibitor of protein kinase A (KT-5720). ATP (100 M) caused a rapid, transient (peak) increase in [Ca2+]i followed by a sustained plateau phase lasting more than 5 minutes. Preincubation of the cells (6 min) with terbutaline, forskolin or 8-Br-cAMP significantly reduced the peak calcium response to ATP. The sustained plateau phase of the response, on the other hand, was augmented by each of the agents. KT-5720 partially reversed the inhibitory effect of terbutaline on the peak and totally inhibited its effect on the plateau phase. These data indicate: (a) that AHF in the bovine eye can be manipulated through cyclic AMP, operating via protein kinase A, (b) that protein kinase A can affect [Ca2+]i homeostasis, (c) that calcium release from the intracellular store, not the entry, affects AHF, and (d) that interaction of [Ca2+]i with cAMP plays a role in modulating AH secretion.

β2 Adrenergic Regulation of the Phagocytic and Microbicide Capacity of Circulating Monocytes: Influence of Obesity and Exercise.

Obese individuals present anomalous immune/inflammatory responses with dysregulations in neuroendocrine responses and immune/stress feedback mechanisms. In this context, exercise and β2 adrenergic activation present monocyte-mediated anti-inflammatory effects that are modulated by obesity. However, these anti-inflammatory effects could immunocompromise the monocyte-mediated innate response against a pathogen challenge. Thus, the objective of this work was to evaluate the effect of obesity, and exercise in this condition, on the β2 adrenergic regulation of the phagocytic and microbicide capacity of circulating monocytes. C57BL/6J mice were allocated to different sedentary or exercised, lean or obese groups. Obese mice showed a lower monocyte-mediated innate response than that of lean mice. Globally, selective β2 adrenergic receptor agonist terbutaline decreased the innate response of monocytes from lean and obese sedentary animals, whereas exercise stimulated it. Exercise modulates β2 adrenergic regulation of the innate response in lean and obese animals, with a global stimulatory or neutral effect, thus abolishing the inhibitory effect of terbutaline occurring in sedentary animals. These effects cannot be explained only by changes in the surface expression of toll-like receptors. Therefore, in general, terbutaline does not hinder the effects of regular exercise, but regular exercise does abolish the effects of terbutaline in sedentary individuals.

Terbutaline, Forskolin and cAMP Reduce Secretion of Aqueous Humor and Inhibit Intracellular Calcium Release in Bovine Cultured Ciliary Epithelium

In order to elucidate the involvement of cyclic AMP and intracellular Ca2+ concentration [Ca2+]i, in the modulation of aqueous humor (AH) secretion, we studied the effects of terbutaline, forskolin and 8‐Br‐cAMP on AH secretion in the isolated intact bovine eye and on ATP‐induced increase in [Ca2+]i in cultured ciliary epithelial (CE) cells. Drug effects on AH secretion were measured by fluorescein dilution. Drug effects on [Ca2+]i were studied by the Fura‐2 fluorescence ratiometric measurement. Terbutaline (100 nmol–100 μM), forskolin (30 nM–100 μM) or 8‐Br‐cAMP (100 nM – 10 μM), administered at fixed concentrations in the arterial perfusate of the intact eye, produced significant reductions in AH secretion. The AH reducing effect of terbutaline was blocked by a selective inhibitor of protein kinase A (KT‐5720). ATP (100 μM) caused a rapid, transient (peak) increase in [Ca2+]i followed by a small but sustained plateau phase lasting more than 5 minutes. Preincubation of the cells (6 min) with terbutaline, forskolin or 8‐Br‐cAMP significantly reduced the peak calcium response to ATP. Each of the drugs, on the other hand, augmented the sustained plateau phase of the calcium response. KT‐5720 partially reversed the inhibitory effect of terbutaline on the peak and totally inhibited its effect on the plateau phase. Taken together, our data support the notion that AH secretion in the bovine eye can be manipulated through cyclic AMP, operating through protein kinase A and that interaction of [Ca2+]i and cAMP may play a role in modulating AH secretion.Support or Funding InformationFight for Sight, London

β2 Adrenergic Regulation of the Phagocytic and Microbicide Capacity of Macrophages from Obese and Lean Mice: Effects of Exercise.

Macrophages are crucial in the inflammation associated with obesity. Exercise is the main non-pharmacological strategy against obesity, not only for improving metabolic impairment, but also because of its anti-inflammatory effects, particularly those mediated by β2 adrenergic receptors (β2-AR). Nevertheless, these anti-inflammatory effects could immunocompromise the innate response against pathogen challenge. Thus, the objective of this work was to evaluate the effect of obesity, and of exercise in this condition, on the β2 adrenergic regulation of the innate function of macrophages. High fat diet-induced obese C57BL/6J mice were used to evaluate the effects of acute and regular exercise on the phagocytic and microbicide capacities of peritoneal macrophages. Selective β2-AR agonist terbutaline (1 µM) decreased the phagocytic and microbicide activities of macrophages from control lean and obese sedentary animals. While acute exercise did not modify the inhibitory capacity of terbutaline, regular exercise abolished this inhibitory effect. These effects cannot be explained only by changes in the surface expression of β2-AR. In conclusion, (1) obesity does not alter the β2-AR-mediated decrease of the innate response of macrophages and (2) regular exercise can revert the inhibitory effect of terbutaline on the phagocytic activity of macrophages, although obesity seems to hinder this immunophysiological adaptation.

Effects of Terbutaline on Growth Performance, Carcass Quality, Some Biochemical Parameters and its Residues in Broiler Chicken.

Terbutaline is a β-agonist that used as growth promoters to improved carcass chemical composition of chicks without residues. The purpose of the present investigation is exploring the effect of different dietary levels and duration of terbutaline on the productive performance, biochemical and carcass quality traits including residue of acres broiler. A total of 150 one-day-old arbor acres broiler chicks were allotted into 5 groups (3 replicates per each). Group 1 was fed on the basal diet without supplement, while groups 2-5 fed on the basal diet supplemented by 5 or 10 mg terbutaline kg-1 diet during 1-42 or 21-42 days, respectively. When handling the dietary levels and duration of terbutaline, results of the present study showed that10 mg terbutaline kg-1 diet during the whole experimental period is a more effective dose for improvement of growth performance with significant (p<0.05) increased serum protein and breast muscles relative weight compared with control. Also, 10 mg terbutaline kg-1 diet during the whole experimental period significantly (p<0.05) increase d CP% (crude protein%) and CHO% (carbohydrate%) of breast muscle and significantly (p<0.05) decreased fat% (ether extract%) of breast muscle and abdominal fat relative weight compared with control. Meanwhile, 5 mg terbutaline kg-1 diet during 1-42 or 21-42 days has no significant effect on the above-mentioned parameters. Regarding residue, the terbutaline residue wasn't detected in broiler meat. It can conclude that 10 mg terbutaline kg-1 diet during the whole experimental period is a better dose and duration for improving growth performance, the chemical composition of breast muscle and carcass traits of broiler chickens with no terbutaline residue in breast muscle.

Modeling the effectiveness of nebulized terbutaline for decompensated chronic obstructive pulmonary disease patients in the emergency department.

Short-acting β2-agonists (SABA) are widely used in the emergency department (ED) to treat patients with decompensated chronic obstructive pulmonary disease (COPD). We sought to model the effectiveness of nebulized SABA (terbutaline) on clinically relevant parameters associated with a reduction in work of breathing or respiratory muscle fatigue in decompensated COPD patients admitted to the ED.Forty consecutive decompensated COPD patients (having received at least one dose of nebulized terbutaline during their stay in the ED) were included in an observational cohort study. The terbutaline dose received at time t was expressed as cumulative dose and as a rate (mg/day). The associations between the terbutaline dose and time-dependent outcome parameters (respiratory rate, heart rate, arterial blood gases, and, as a marker of terbutaline's systemic effect, serum potassium) were analyzed using a nonlinear, mixed-effects model. The effect of various covariates influencing terbutaline's effectiveness (baseline characteristics and concomitant treatments) was assessed on the model.Among the investigated patients, a total of 377 time-dependent observations were available for analysis. Neither the cumulative dose nor the dose rate at time t significantly influenced the arterial blood gas parameters or heart rate. The cumulative dose of terbutaline was associated with a lower serum potassium level (P < 0.001) and, less significantly, a lower respiratory frequency (P = 0.036). In a tertile analysis, the need for post-ED hospitalization was not associated with the cumulative dose or dose rate of terbutaline.Overall, the results of our modeling study strongly suggest that terbutaline dose did not influence time-dependent outcomes other than serum potassium, and thus call into question the systematic administration of inhaled SABA to patients admitted to the ED for decompensated COPD.

R- and S-terbutaline activate large conductance and Ca2 + dependent K+ (BKCa) channel through interacting with β2 and M receptor respectively

This study investigated the effect of the β2 receptor agonist terbutaline on the single channel activity of BKCa channel. The effects of racemate and two isomers of terbutaline were all assessed. β2 adrenoceptors were stably overexpressed on HEK293 cells by lentiviral transduction method and chicken BKCa channels were transiently expressed on normal HEK293 cell line or HEK293 cells overexpressing β2 receptors. Data showed that terbutaline significantly increased the single channel open probability of BKCa channel within 10min. The channel activating effects of terbutaline are stereoselective and mainly stay with the R-enantiomers. The opening probability of BKCa channel at 10min after drug application normalized to that just before drug application (Po10/Po0s) for R- and S-terbutaline were 7.85±3.20 and 1.06±0.45 respectively at 1μM concentration, corresponding to 28.37±9.96 and 2.68±1.09 at the higher concentration of 10μM. ICI 118551 blocked the effect of R- but not S-terbutaline (10μM), whereas atropine blocked the channel activating effects of S-terbutaline of higher concentration. In addition, the muscarinic receptor agonist carbachol increased the BKCa channel activity in an atropine-sensitive manner as an positive control experiment, which indicate the involvement of M receptor in the channel activating effect of S-terbutaline.

The β2‐Adrenoceptor Agonist Terbutaline Stimulates Angiogenesis via Akt and ERK Signaling

Angiogenesis is associated with changes in endothelial cell (EC) proliferation and tube formation, controlled by extracellular receptor-activated kinase (ERK)/mitogen activated protein kinase (MAPK) and Akt signaling. Important regulators of these systems include hormones acting on G-protein-coupled receptors, such as beta 2-adrenoceptors (β2-ARs). In central nervous system (CNS) trauma, the importance of β2-AR modulation has been highlighted, although the effects on revascularization remain unclear. Vascular protection and revascularization are, however, key to support regeneration. We have investigated the angiogenic capacity of the specific β2-AR agonist terbutaline on ECs derived from the CNS, namely bEnd.3-cells. As angiogenesis is a multistep process involving increased proliferation and tube formation of ECs, we investigated the effects of terbutaline on these processes. We show that terbutaline significantly induced bEnd.3 tube formation in a matrigel in vitro assay. Moreover, administration of specific inhibitors of ERK and Akt signaling both inhibited terbutaline-induced tube formation. The proliferation rate of the ECs was not affected. In order to investigate the general effects of terbutaline in an organotypic system, we have used the chick chorioallantoic membrane (CAM)-assay. Most importantly, terbutaline increased the number of blood vessels in this in ovo setting. Although we observed a positive trend, the systemic administration of terbutaline did not significantly improve the functional outcome, nor did it affect revascularization in our spinal cord injury model. In conclusion, these data indicate that terbutaline is promising to stimulate blood vessel formation, underscoring the importance of further research into the angiotherapeutic relevance of terbutaline and β2-AR signaling after CNS-trauma. J. Cell. Physiol. 232: 298-308, 2017. © 2016 Wiley Periodicals, Inc.

Effect of phenylephrine and terbutaline on ischemic priapism: a retrospective review

BackgroundIschemic priapism is the most common cause of priapism due to low blood flow. Current guidelines recommend penile aspiration and the use of intracavernous injection of vasoactive agents. The data to support these recommendations are limited and rely on expert consensus. ObjectiveThe objective was to determine the effectiveness of terbutaline and phenylephrine on detumescence of ischemic priapism. MethodsThis was a retrospective review of patients presenting to the emergency department with a chief concern of priapism who received oral or subcutaneous terbutaline or intracavernous phenylephrine. The primary outcome is successful detumescence. The secondary outcome is drug-related adverse drug events. ResultsA total of 31 cases of ischemic priapism were included, with 8 patients receiving terbutaline and 23 receiving phenylephrine. Of the cases treated with terbutaline, 25% had successful detumescence compared with phenylephrine with a 74% success rate. No drug-related adverse events were reported or identified. ConclusionsPatients receiving intracavernous irrigation with phenylephrine were more likely to achieve successful detumescence than those treated with oral or subcutaneous terbutaline.

Success rate of terbutaline in inhibiting preterm labor for 48 h

Objective: To determine terbutaline success rate in postponing preterm labor for 48 h and to identify factors associated with its efficacy, side effects, maternal and neonatal outcomes.Methods: A retrospective study analyzing data from pregnant women suffering from preterm labor who had received terbutaline for inhibition of labor from January 2007 to December 2013.Results: A total of 385 cases were analyzed; there were 321 cases (83.4%) delivered ≥48 h and 64 cases (16.6%) delivered before 48 h. The factors that affect the success rate of terbutaline administration in singleton pregnancy were cervical dilatation (ORs 0.37; 95% CI 0.18–0.79) and cervical effacement (ORs 0.36; 95% CI 0.17–0.75). The most common side effect of terbutaline was tachycardia (95.1%), but there were no serious cardiovascular events and maternal death. Mean neonatal birth weight was 2.294.3 ± 638.4 g. Neonatal complications included respiratory distress syndrome (RDS) 16.2%, intraventricular hemorrhage (IVH) 1.4%, necrotizing enterocolitis (NEC) 0.7%, sepsis 5.3%, and neonatal death 0.9%.Conclusions: The success rate of terbutaline in treatment of preterm labor was high whereas side effects were tolerable. Neonatal outcome was good. The factors that significantly affect the success rate of terbutaline administration in singleton pregnancy were cervical dilatation and cervical effacement. Thus, terbutaline can be used safely for short-term treatment of preterm labor.

Repurpose terbutaline sulfate for amyotrophic lateral sclerosis using electronic medical records.

Prediction of new disease indications for approved drugs by computational methods has been based largely on the genomics signatures of drugs and diseases. We propose a method for drug repositioning that uses the clinical signatures extracted from over 13 years of electronic medical records from a tertiary hospital, including >9.4 M laboratory tests from >530,000 patients, in addition to diverse genomics signatures. Cross-validation using over 17,000 known drug–disease associations shows this approach outperforms various predictive models based on genomics signatures and a well-known “guilt-by-association” method. Interestingly, the prediction suggests that terbutaline sulfate, which is widely used for asthma, is a promising candidate for amyotrophic lateral sclerosis for which there are few therapeutic options. In vivo tests using zebrafish models found that terbutaline sulfate prevents defects in axons and neuromuscular junction degeneration in a dose-dependent manner. A therapeutic potential of terbutaline sulfate was also observed when axonal and neuromuscular junction degeneration have already occurred in zebrafish model. Cotreatment with a β2-adrenergic receptor antagonist, butoxamine, suggests that the effect of terbutaline is mediated by activation of β2-adrenergic receptors.

Estrogen modulates β2-adrenoceptor-induced cell-mediated and inflammatory immune responses through ER-α involving distinct intracellular signaling pathways, antioxidant enzymes, and nitric oxide

Sympathetic noradrenergic neuronal activity in the lymphoid organs regulates immunity through the release and binding of norepinephrine to β2-adrenergic receptors (AR) on lymphocytes. In women, estrogen modulates immune responses during menstrual cycles, and in aging and age-associated diseases. The intent of the present study is to characterize the extent of immunomodulation by β2-AR in the presence of estrogen and the involvement of intracellular signaling mechanisms including the role of antioxidant enzymes (AOE) in lymphocytes. In vitro effects of terbutaline, β2-AR agonist, either alone or in combination with 17β-estradiol (E2) were examined on splenocyte proliferation, cytokine (IFN-γ, IL-2, and IL-6) production, intracellular signaling molecules (p-ERK, p-CREB, p-Akt, and p-NF-κB) expression, NO production, and AOE activities [superoxide dismutase (SOD), catalase, and glutathione peroxidase (GPx)]. The specificity of their actions was investigated using β-AR antagonist, and inhibitors of signaling targets and inducible nitric oxide synthase (iNOS). Terbutaline suppressed T cell proliferation and IL-6 production and increased AOE activities involving ERK, PKA, PKC, and NF-κB pathways and NO production. E2 alone enhanced T cell proliferation and decreased IL-6 production and NF-κB expression through ER-α. E2 in the presence of terbutaline reversed terbutaline-induced effects on T cell proliferation, IL-6 production, p-ERK and p-CREB expression, AOE activities, NO production, and NF-κB expression. Estrogen through ER-α differentially modulates β2-AR-induced immune responses involving ERK, PKA, PKC, and NF-κB pathways, and NO that may be responsible for estrogen-induced immunosenescence and development of female-specific diseases.

The β2 -adrenoceptor agonist terbutaline recovers rat pharyngeal dilator muscle force decline during severe hypoxia.

Obstructive sleep apnoea syndrome (OSAS) is a debilitating condition characterized by recurrent occlusions of the pharyngeal airway during sleep accompanied by arterial hypoxaemia. Upper airway muscle dysfunction is implicated in the pathophysiology of OSAS. Pharmacological agents that improve muscle contractile and endurance properties may have therapeutic value. We tested the hypothesis that the β(2) -adrenoceptor agonist terbutaline improves rat sternohyoid muscle performance especially during hypoxic stress. Isometric contractile and endurance properties were examined ex vivo in Krebs solution at 35°C. Muscles were incubated in tissue baths under hyperoxic (95% O(2) /5% CO(2)) conditions in the absence (control) or presence of the β(2) -adrenoceptor agonist terbutaline (1 μM). In additional experiments under hypoxic (95% N(2) /5% CO(2)) conditions, the effects of terbutaline were examined in the presence of the β-adrenoceptor antagonist propranolol (1 μM). Hypoxia significantly impaired sternohyoid force production. Terbutaline completely recovered hypoxic depression of force, an effect that was blocked by co-application with propranolol. The β(2) -adrenoceptor agonist terbutaline completely recovers hypoxic depression of upper airway muscle force. β(2) -adrenoceptor agonists warrant investigation in animal models of OSAS reporting upper airway and diaphragm muscle dysfunction.