SR59230A
目录号 : GC39725
A β3-AR antagonist
Cas No.:174689-39-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
SR 59230A (hydrochloride) is a β3-adrenergic receptor (β3-AR) antagonist (pA2s = 8.76, 7.31, and 6.63 in rat proximal colon, guinea pig atrium, and guinea pig trachea, respectively).1 It is less selective for β3-AR in cells transfected with the human β-AR subtypes (Kis = 16.4, 61.9, and 122 nM for β1-, β2-, and β3-AR, respectively).2 At low concentrations, SR 59230A blocks MDMA-induced hyperthermia, while at high concentrations it blocks hyperthermia but also increases heat loss through an α1-AR antagonistic mechanism.3 In adipocytes, it induces phosphorylation of p38 MAPK via the Gs pathway.4 It has also been used in studies of heart failure to elucidate the role of the β3-ARs.5
1.Manara, L., Badone, D., Baroni, M., et al.Functional identification of rat atypical β-adrenoceptors by the first β3-selective antagonists, aryloxypropanolaminotetralinsBr. J. Pharmacol.117(3)435-442(1996) 2.Hoffman, C., Leitz, M.R., Oberdorf-Maass, S., et al.Comparative pharmacology of human β-adrenergic receptor subtypes--characterization of stably transfected receptors in CHO cellsNaunyn-Schmiedeberg's Arch. Pharmacol.369(2)151-159(2004) 3.Bexis, S., and Docherty, J.R.Role of α1- and β3-adrenoceptors in the modulation by SR59230A of the effects of MDMA on body temperature in the mouseBr. J. Pharmacol.158(1)259-266(2009) 4.Mizuno, K., Kanda, Y., Kuroki, Y., et al.Stimulation of β3-adrenoceptors causes phosphorylation of p38 mitogen-activated protein kinase via a stimulatory G protein-dependent pathway in 3T3-L1 adipocytesBr. J. Pharmacol.135(4)951-960(2002) 5.Gan, R.T., Li, W.M., Xiu, C.H., et al.Chronic blocking of β3-adrenoceptor ameliorates cardiac function in rat model of heart failureChin. Med. J. (Engl.)120(24)2250-2255(2007)
| Cas No. | 174689-39-5 | SDF | |
| Canonical SMILES | O[C@@H](CN[C@H]1CCCC2=C1C=CC=C2)COC3=CC=CC=C3CC.O=C(O)C(O)=O | ||
| 分子式 | C23H29NO6 | 分子量 | 415.48 |
| 溶解度 | DMSO: 31.25 mg/mL (75.21 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.4069 mL | 12.0343 mL | 24.0685 mL |
| 5 mM | 0.4814 mL | 2.4069 mL | 4.8137 mL |
| 10 mM | 0.2407 mL | 1.2034 mL | 2.4069 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Brown Adipocyte ADRB3 Mediates Cardioprotection via Suppressing Exosomal iNOS
Circ Res 2022 Jul 8;131(2):133-147.PMID:35652349DOI:10.1161/CIRCRESAHA.121.320470.
Background: The ADRB3 (β3-adrenergic receptors), which is predominantly expressed in brown adipose tissue (BAT), can activate BAT and improve metabolic health. Previous studies indicate that the endocrine function of BAT is associated with cardiac homeostasis and diseases. Here, we investigate the role of ADRB3 activation-mediated BAT function in cardiac remodeling. Methods: BKO (brown adipocyte-specific ADRB3 knockout) and littermate control mice were subjected to Ang II (angiotensin II) for 28 days. Exosomes from ADRB3 antagonist SR59230A (SR-exo) or agonist mirabegron (MR-exo) treated brown adipocytes were intravenously injected to Ang II-infused mice. Results: BKO markedly accelerated cardiac hypertrophy and fibrosis compared with control mice after Ang II infusion. In vitro, ADRB3 KO rather than control brown adipocytes aggravated expression of fibrotic genes in cardiac fibroblasts, and this difference was not detected after exosome inhibitor treatment. Consistently, BKO brown adipocyte-derived exosomes accelerated Ang II-induced cardiac fibroblast dysfunction compared with control exosomes. Furthermore, SR-exo significantly aggravated Ang II-induced cardiac remodeling, whereas MR-exo attenuated cardiac dysfunction. Mechanistically, ADRB3 KO or SR59230A treatment in brown adipocytes resulted an increase of iNOS (inducible nitric oxide synthase) in exosomes. Knockdown of iNOS in brown adipocytes reversed SR-exo-aggravated cardiac remodeling. Conclusions: Our data illustrated a new endocrine pattern of BAT in regulating cardiac remodeling, suggesting that activation of ADRB3 in brown adipocytes offers cardiac protection through suppressing exosomal iNOS.
β3 adrenergic receptor antagonist SR59230A exerts beneficial effects on right ventricular performance in monocrotaline-induced pulmonary arterial hypertension
Exp Ther Med 2020 Jan;19(1):489-498.PMID:31853320DOI:10.3892/etm.2019.8236.
Pulmonary arterial hypertension (PAH) is a progressive disease with a high mortality rate. Previous studies have revealed the important function of the β3 adrenergic receptor (β3-AR) in cardiovascular diseases, and the potential beneficial effects of numerous β3-AR agonists on pulmonary vasodilation. Conversely, a number of studies have proposed that the antagonism of β3-AR may prevent heart failure. The present study aimed to investigate the functional involvement of β3-AR and the effects of the β3-AR antagonist, SR59230A, in PAH and subsequent heart failure. A rat PAH model was established by the subcutaneous injection of monocrotaline (MCT), and the rats were randomly assigned to groups receiving four weeks of SR59230A treatment or the vehicle control. SR59230A treatment significantly improved right ventricular function in PAH in vivo compared with the vehicle control (P<0.001). Additionally, the expression level of β3-AR was significantly upregulated in the lung and heart tissues of PAH rats compared with the sham group (P<0.01), and SR59230A treatment inhibited this increase in the lung (P<0.05), but not the heart. Specifically, SR59230A suppressed the elevated expression of endothelial nitric oxide and alleviated inflammatory infiltration to the lung under PAH conditions. These results are, to the best of our knowledge, the first to reveal that SR59230A exerts beneficial effects on right ventricular performance in rats with MCT-induced PAH. Furthermore, blocking β3-AR with SR59230A may alleviate the structural changes and inflammatory infiltration to the lung as a result of reduced oxidative stress.
SR59230A, a beta-3 adrenoceptor antagonist, inhibits ultradian brown adipose tissue thermogenesis and interrupts associated episodic brain and body heating
Am J Physiol Regul Integr Comp Physiol 2011 Oct;301(4):R987-94.PMID:21813867DOI:10.1152/ajpregu.00085.2011.
Brown adipose tissue (BAT) thermogenesis occurs episodically in an ultradian manner approximately every 80-100 min during the waking phase of the circadian cycle, together with highly correlated increases in brain and body temperatures, suggesting that BAT thermogenesis contributes to brain and body temperature increases. We investigated this in conscious Sprague-Dawley rats by determining whether inhibition of BAT thermogenesis via blockade of beta-3 adrenoceptors with SR59230A interrupts ultradian episodic increases in brain and body temperatures and whether SR59230A acts on BAT itself or via sympathetic neural control of BAT. Interscapular BAT (iBAT), brain, and body temperatures, tail artery blood flow, and heart rate were measured in unrestrained rats. SR59230A (1, 5, or 10 mg/kg ip), but not vehicle, decreased iBAT, body, and brain temperatures in a dose-dependent fashion (log-linear regression P < 0.01, R(2) = 0.3, 0.4, and 0.4, respectively, n = 10). Ultradian increases in BAT, brain, and body temperature were interrupted by administration of SR59230A (10 mg/kg ip) compared with vehicle, resuming after 162 ± 24 min (means ± SE, n = 10). SR59230A (10 mg/kg ip) caused a transient bradycardia without any increase in tail artery blood flow. In anesthetized rats, SR59230A reduced cooling-induced increases in iBAT temperature without affecting cooling-induced increases in iBAT sympathetic nerve discharge. Inhibition of BAT thermogenesis by SR59230A, thus, reflects direct blockade of beta-3 adrenoceptors in BAT. Interruption of episodic ultradian increases in body and brain temperature by SR59230A suggests that BAT thermogenesis makes a substantial contribution to these increases.
Agonistic activity of SR59230A at atypical beta-adrenoceptors in guinea pig gastric fundus and duodenum
Eur J Pharmacol 2001 Mar 23;416(1-2):165-8.PMID:11282126DOI:10.1016/s0014-2999(01)00854-8.
We have recently suggested that atypical beta-adrenoceptors are present in guinea pig gastric fundus and duodenum. In the present study, we have shown that SR59230A (3-(2-ethylphenoxy)-1-[(1S)-1,2,3,4-tetrahydronaphth-1-ylamino]-(2S)-2-propanol oxalate), a selective beta(3)-adrenoceptor antagonist, possesses agonistic activities at atypical beta-adrenoceptors in these tissues. SR59230A caused concentration-dependent relaxations. However, (+/-)-propranolol (1 microM) did not affect SR59230A-induced relaxations. Pretreatment of with a combination of (+/-)-propranolol (1 microM) and the non-selective beta(1)-, beta(2)-, beta(3)- and beta(4)-adrenoceptor antagonist, (+/-)-bupranolol (30 microM), significantly antagonized the relaxant effects induced by SR59230A. The results clearly indicate that SR59230A acts as an atypical beta-adrenoceptor agonist on guinea pig gastric fundus and duodenum.
SR59230A blocks beta3-adrenoceptor-linked modulation of upcoupling protein-1 and leptin in rat brown adipocytes
Eur J Pharmacol 1998 Jul 3;352(1):125-9.PMID:9718277DOI:10.1016/s0014-2999(98)00404-x.
Experimental evidence suggests that, by stimulating energy expenditure in brown fat, selective beta3-adrenoceptor agonists can reduce body weight in obese rodents. In order to investigate further the physiological role of beta3-adrenoceptors in brown adipocytes, we analysed the effects of selective beta3-adrenoceptor agonists and antagonists on uncoupling protein-1 and leptin gene expression in culture-differentiated brown fat cells. Our main findings were that: (i) the leptin gene is expressed in brown adipocytes; (ii) the selective beta3-adrenoceptor agonist, N[(2S)-7-carbethoxy-1,2,3,4-tetrahydronaphth-2-yl]-(2R)-2-hydroxy- 2-(3-chlorophenil)ethanamine hydrochloride (SR58611A), inhibits leptin gene while inducing uncoupling protein-1 gene expression; (iii) these opposite effects of SR58611A are antagonized by the selective beta3-adrenoceptor antagonist, SS-enantiomer 3-(2-ethylphenoxy)-1-(1S),2,3,4-tetrahydronaphth-1-ylamin ol]-(2S)-2-propanol oxalate (SR59230A), but not by the selective beta1-adrenoceptor antagonist (+/-)-[2-(3-carbamoyl-4-hydroxyphenoxy)-ethylamino]-3-[4(1-methyl- 4-trifluoromethyl-2-imidazolyl)-phenoxy]-2 propanol (CGP20712A); and (iv) these effects are due to increased cyclic AMP levels. These results confirm by means of a different experimental approach that beta3-adrenoceptors play a central role in controlling the expression of genes that are important for brown fat function.