U-73122 is a potent and selective phospholipase C (PLC) inhibitor with an IC50 value of approximately 1-2.1µM. It also inhibits 5-lipoxygenase (5-LO)[1]. U-73122 can inhibit Ca2+ release from the intracellular sarcoplasmic reticulum by inhibiting the Ca2+ pump[2]. U-73122 is a potent inhibitor of the smooth muscle endoplasmic reticulum calcium ATPase (SERCA) pump [3].
In vitro, treatment of human osteosarcoma MG-63 cells with U-73122 (1, 10µM) for 24h reduced cell number and cell-cell adhesion, significantly changed cell morphology, and rearranged the expression group of PLC enzymes [4]. Treatment of UMR-106 cells with U-73122 (0.2-10µM) for 3min dose-dependently inhibited calcium transients stimulated by endothelin-1 and parathyroid hormone[5]. U-73122 (2-12µM) treatment of β-TC3 cells dose-dependently inhibited the effects of carbachol on intracellular free calcium and insulin release[6].
In vivo, U-73122 (9mg/kg) treated wild-type mice by intraperitoneal injection for 15min significantly reduced cardiac TNF-α expression[7].
References:
[1] Sarabia-Sánchez M A, Moreno-Londoño A P, Castañeda-Patlán M C, et al. Non-canonical Wnt/Ca2+ signaling is essential to promote self-renewal and proliferation in colon cancer stem cells[J]. Frontiers in Oncology, 2023, 13: 1121787.
[2] Macmillan D, McCarron J G. The phospholipase C inhibitor U‐73122 inhibits Ca2+ release from the intracellular sarcoplasmic reticulum Ca2+ store by inhibiting Ca2+ pumps in smooth muscle[J]. British journal of pharmacology, 2010, 160(6): 1295-1301.
[3] Hollywood M A, Sergeant G P, Thornbury K D, et al. The PI‐PLC inhibitor U‐73122 is a potent inhibitor of the SERCA pump in smooth muscle[J]. British journal of pharmacology, 2010, 160(6): 1293-1294.
[4] Lo Vasco V R, Leopizzi M, Di Maio V, et al. U-73122 reduces the cell growth in cultured MG-63 ostesarcoma cell line involving Phosphoinositide-specific Phospholipases C[J]. Springerplus, 2016, 5(1): 156.
[5] Tatrai A, Suk K L, Stern P H. U-73122, a phospholipase C antagonist, inhibits effects of endothelin-1 and parathyroid hormone on signal transduction in UMR-106 osteoblastic cells[J]. Biochimica et Biophysica Acta (BBA)-Molecular Cell Research, 1994, 1224(3): 575-582.
[6] Chen T H, Hsu W H. U-73122 inhibits carbachol-induced increases in [Ca2+] i, IP3, and insulin release in β-TC3 cells[J]. Life sciences, 1994, 56(5): 103-108.
[7] Peng T, Shen E, Fan J, et al. Disruption of phospholipase Cγ1 signalling attenuates cardiac tumor necrosis factor-α expression and improves myocardial function during endotoxemia[J]. Cardiovascular research, 2008, 78(1): 90-97.
U-73122是有效的、选择性的磷脂酶C（PLC）抑制剂，IC50值约为1-2.1µM，也可抑制5-脂氧合酶（5-LO）[1]。U-73122可以通过抑制Ca2+泵来抑制细胞内肌浆网中的Ca2+释放[2]。U-73122是平滑肌肌内质网钙ATP酶（SERCA）泵的有效抑制剂[3]
在体外，U-73122（1、10µM）处理人骨肉瘤MG-63细胞24h，减少了细胞数量和细胞间粘附，细胞形态显著变化，PLC酶的表达组发生了重排[4]。U-73122（0.2-10µM）处理UMR-106细胞3min，剂量依赖性地抑制了内皮素-1和甲状旁腺激素刺激的钙瞬变[5]。U-73122（2-12µM）处理β-TC3细胞，剂量依赖性地抑制了卡巴胆碱对细胞内游离钙和胰岛素释放的影响[6]。
在体内，U-73122（9mg/kg）通过腹腔注射处理野生型小鼠15min，显著降低了心脏TNF-α表达[7]。