Terbutaline

Terbutaline is a novel selective β2-adrenergic receptor agonist. Terbutaline can dilate bronchial smooth muscle by activating adenylate cyclase to increase intracellular cyclic adenosine monophosphate (cAMP) levels. Terbutaline reduces smooth muscle contraction and inflammation by activating protein kinase A (PKA) and inhibiting myosin light chain kinase (MLCK). Terbutaline is used for research on asthma, chronic obstructive pulmonary disease (COPD), and preterm labor^[1-4].

In vitro, Terbutaline (10μM) repeatedly activated CD3+ T cells (for 48h each time; 4 times in total). Terbutaline had no significant effect on the expression of T cell exhaustion markers (CD4⁺TIM-3⁺CD38⁺ and CD8⁺TIM-3⁺CD38⁺) or cytotoxicity^[5]. Terbutaline (0.1nM–10μM) was pretreated on J774 mouse macrophages for 30min, followed by stimulation with LPS (10ng/mL) for 1h. Terbutaline significantly inhibited the phosphorylation of p38 MAPK and reduced TNF production^[6].

In vivo, Terbutaline (1–10μg; 5μL) was administered to male Hsd: CD-1 (ICR) mice via intrathecal injection (i.t.; single dose). Terbutaline significantly increased blood glucose levels and plasma corticosterone levels^[7]. Terbutaline (500μg/kg/day; twice daily) was intraperitoneally injected into collagen-induced arthritis (CIA) DBA1/J mice for 16 days. Terbutaline significantly alleviated arthritis symptoms in CIA mice, reduced the histopathological injuries of the ankle joints, decreased the arthritis score of the four limbs, and reduced the thickness of the ankle joints and rear paws^[8].

References:
[1] Mohamed Ismail NA, Ibrahim M, Mohd Naim N, et al. Nifedipine versus terbutaline for tocolysis in external cephalic version. Int J Gynaecol Obstet. 2008 Sep;102(3):263-6.
[2] Loureiro JA, Andrade S, Ramalho MJ, et al. The interaction of a β2 adrenoceptor agonist drug with biomimetic cell membrane models: The case of terbutaline sulphate. Life Sci. 2021 Nov 15;285:119992.
[3] Karni R, Mizrachi S, Reiss-Sklan E, et al. The pp60c-Src inhibitor PP1 is non-competitive against ATP. FEBS Lett. 2003 Feb 27;537(1-3):47-52.
[4] Choucair-Jaafar N, Salvat E, Freund-Mercier MJ, et al. The antiallodynic action of nortriptyline and terbutaline is mediated by β(2) adrenoceptors and δ opioid receptors in the ob/ob model of diabetic polyneuropathy. Brain Res. 2014 Feb 10;1546:18-26.
[5] Hajiaghayi M, Gholizadeh F, Rahbari N, et al. Nebivolol prevents exhausted T cells and enhances cytotoxicity against MCF-7 breast cancer cells in a β2-adrenergic receptor-dependent manner. Clin Exp Immunol. 2026 Jan 6;220(1):uxag018.
[6] Keränen T, Hömmö T, Hämäläinen M, et al. Anti-Inflammatory Effects of β2-Receptor Agonists Salbutamol and Terbutaline Are Mediated by MKP-1. PLoS One. 2016 Feb 5;11(2):e0148144.
[7] Sim YB, Park SH, Kim SS, et al. Spinal β-adrenergic receptors' activation increases the blood glucose level in mice. Anim Cells Syst (Seoul). 2017 Jul 10;21(4):278-285.
[8] Lu JH, Rui XX, Wang TT, et al. Activation of β2-adrenergic Receptor Alleviates Collagen-induced Arthritis by Ameliorating Th17/Treg Imbalance. Iran J Immunol. 2023 Mar 14;20(1):16-25.

Terbutaline是一种新型的选择性肾上腺素β2受体激动剂。Terbutaline可通过激活腺苷酸环化酶增加细胞内环磷酸腺苷（cAMP）水平来舒张支气管平滑肌，通过激活蛋白激酶A（PKA）并抑制肌球蛋白轻链激酶（MLCK）以减少平滑肌收缩和炎症反应。Terbutaline可用于哮喘、慢性阻塞性肺疾病（COPD）和早产的相关研究^[1-4]。

在体外，Terbutaline（10μM）反复激活CD3⁺ T细胞（每次48小时；共4次）。对T细胞耗竭标志物（CD4⁺TIM-3⁺CD38⁺和CD8⁺TIM-3⁺CD38⁺）的表达及细胞毒性均无显著影响^[5]。Terbutaline（0.1nM-10μM）预处理J774小鼠巨噬细胞30min，随后以LPS（10ng/ml）刺激1h。Terbutaline显著抑制p38 MAPK的磷酸化，同时降低TNF的产生^[6]。

在体内，Terbutaline（1-10μg；5μl）通过鞘内注射（i.t.；单次）给药于雄性Hsd: CD-1 (ICR)小鼠。Terbutaline显著提高了血糖水平，同时增加了血浆皮质酮水平^[7]。Terbutaline（500μg/kg/day；每日两次）腹腔注射于关节炎（CIA）DBA1/J小鼠16天。Terbutaline显著缓解了CIA小鼠的关节炎症状，减轻了踝关节的组织病理学损伤、降低了四肢关节炎评分以及减小了踝关节和后爪的厚度^[8]。