| 名稱 | BMY 7378 dihydrochloride |
| 描述 | BMY 7378 dihydrochloride (BMY7378 HCl) , α1D-adrenergic receptor antagonist, is a weak partial agonist/antagonist of 5-HT1A receptor. |
| 激酶實(shí)驗(yàn) | Phosphatase activities are determined on immunoprecipitates of the phosphatases. Briefly, 2×106 K562 cells are treated for 18 hr with Salubrinal (20 μM), PSI (10 nM), the combination of both drugs or okadaic acid (100 nM). After washing with PBS, cells are lysed for 15 min on ice either in PP1LB (for determination of PP1γ-activity; 20 mM Tris-HCl, pH 7.5, 1% Triton X-100, 10% glycerol, 132 mM NaCl, Roche complete protease inhibitor ) or in RIPA (for PP2A), supplemented with Roche complete protease inhibitor). Cell lysates containing 500 μg (PP1γ) or 300 μg (PP2A) protein are immunoprecipitated overnight at 4°C with 2-3 μg of the appropriate antibodies and then incubated with Protein A-Sepharose. Immunoprecipitates are washed three times in lysis buffer, followed by resuspension in phosphatase assay buffer (PP2A: 20 mM Tris-HCl, pH7.5, 0.1 mM CaCl2; PP1γ: 50 mM Tris HCl pH 7.0, 0.2 mM MnCl2, 0.1 mM CaCl2, 125 μg/mL BSA, 0.05% Tween 20), supplemented with 100 μM 6,8-difluoro-4-methyl-umbelliferyl phosphate (DiFMUP). Precipitates are allowed to react with substrate for 1 hr at 37°C on an Eppendorf Thermoshaker, centrifuged and DiFMU fluorescence is measured on a BioTek Lambda Fluoro 320 microplate reader (360 nmex/460 nmem). Phosphatase activities are given as percent change relative to the control (DMSO treated cells)[1]. |
| 體外活性 | 在大鼠體內(nèi),BMY7378（0.25-5 mg/kg,s.c.）劑量依賴性降低8-OH-DPAT（0.75 mg/kg,s.c.）誘導(dǎo)的前爪踩踏和頭部搖晃.在麻醉大鼠的腹側(cè)海馬體中,大鼠體內(nèi)微量滲析檢測顯示,BMY7378使5-HT釋放出現(xiàn)劑量依賴性的顯著減少.BMY7378 (pA2為8.67)與去甲腎上腺素作用可使大鼠主動(dòng)脈收縮,效果比育亨賓 (pA2為6.62)高約100倍.BMY7378 (pA2：6.48)會(huì)拮抗人體隱靜脈(α2C-腎上腺素受體)中去甲腎上腺素引起的收縮響應(yīng),效果比育亨賓(pA2為7.56)低10倍. |
| 體內(nèi)活性 | BMY7378對α1D-腎上腺素受體亞型的作用有選擇性{PKi: α1b-腎上腺素受體6.2（倉鼠）,7.2（人）；α1c-腎上腺素受體 6.1（牛）,6.6（人）；α1d-腎上腺素受體8.2（大鼠）,9.4（人）}。BMY7378對α2c-腎上腺素受體的選擇性（pKi：6.54）是其他α2-腎上腺素受體的10倍。在大鼠中縫背核中,BMY7378（1-30 nM）具有劑量依賴性的抑制作用。 |
| 存儲(chǔ)條件 | Powder: -20°C for 3 years | In solvent: -80°C for 1 year | Shipping with blue ice. |
| 溶解度 | Ethanol : 16 mg/mL (34.9 mM)
DMSO : 85 mg/mL (185.4 mM)
H2O : 84 mg/mL (183.2 mM)
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| 關(guān)鍵字 | BMY 7378 dihydrochloride | BMY-7378 Dihydrochloride | Adrenergic Receptor | spontaneously hypertensive rats | 5-hydroxytryptamine Receptor | BMY7378 | alpha 1-adrenoceptor | BMY7378 Dihydrochloride | selective | BMY-7378 | inhibit | Serotonin Receptor | 5-HT1A receptor | Beta Receptor | 5-HT Receptor | Inhibitor | BMY 7378 Dihydrochloride | BMY 7378 |
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