Isoprenaline hydrochloride (NCI-c55630) is a potent beta-adrenergic agonist with the peripheral vasodilator, bronchodilator, and cardiac stimulating properties.

用 Isoprenaline （300 nM，3 分钟）诱导完整的大鼠脂肪细胞，可使微粒 cGMP 和西洛他胺抑制的低 Km cAMP 磷酸二酯酶（cAMP-PDE）活性分别提高约 50%和 100%[1]。环 GMP PDE（PDE 3）抑制剂西洛他胺（100 nM）可增强 Isoprenaline 诱导的松弛。 Isoprenaline （5 nM 和 10 microM）可增加环 AMP 水平，西洛他胺（10 microM）、环 AMP PDE（PDE 4）抑制剂罗利普仑（10 microM）和环 GMP 诱导剂（50 nM ANF 或 30 nM SNP 加 100 nM DMPPO）可增强这种效应[2]。 Isoprenaline 增加了 Akt 以及下游 FoxO1、FoxO3a 和 CREB 的磷酸化水平。当儿茶酚胺与β肾上腺素受体结合时，G蛋白偶联受体激酶-2（GRK2）介导PI3K向β肾上腺素受体转位，然后增强β-arrestin和AP-2的招募，最终导致β肾上腺素受体的内化和下调。有报道称，通过置换 I 类 PI3K 同工酶来破坏 PI3K 和 GRK2 之间的相互作用可阻止激动剂刺激的 β 肾上腺素受体内化 [3]。

方法：为诱导病理性心脏重塑模型，将 Isoprenaline hydrochloride (1.5 mg/kg in NaCl 0.9%) 皮下注射给 C57BL/6 小鼠，每天一次，持续十天。
结果：在给药 Isoprenaline 的小鼠中出现了心脏结构异常 (IVSTd 和 LVPWd 增加)、心功能受损 (EF 和 CO) 和心重/体重比升高 (HW/BW)。[3]

Cells are seeded in 24-well culture dishes at a density of 2 to 5×10^4 cells per well. Experiments are performed after 3 to 5 days in culture when cells has reached confluence. Culture medium is aspirated and replaced by 0.5 mL of PBS containing the pharmacological agents. Treatments are performed in quadruplicate at 37°C. The type 3, 4 and 5 PDE inhibitors cilostamide (10 gM), rolipram (10 pM) and DMPPO (10 gM), respectively, are incubated with cells for 30 min before addition of adenylate or guanylate cyclase activators. Cyclic GMP and cyclic AMP are respectively increased in RASMC by stimulation of particulate guanylate cyclase with ANF (50 nM for 10 min) or fl-adrenoceptors with isoprenaline (5 nm for 5 min). At the end of the incubation period, the medium is removed and intracellular cyclic nucleotides are extracted by two ethanolic (65%) ishes at 4°C for 5 min. Ethanolic extracts are pooled, evaporated to dryness by a Speed-Vac system. The dried extract is dissolved in a suitable amount of assay buffer and cyclic nucleotide levels are measured by scintillation proximity assay [3].