Alprostadil functions as a prostanoid receptor ligand, exhibiting binding affinities Kis of 1.1 nM, 2.1 nM, 10 nM, 33 nM, and 36 nM for murine EP3, EP4, EP2, IP, and EP1, correspondingly. Alprostadil can inhibit platelet aggregation and thrombin A2 production, and has diuretic and renal function protection [1-3].
Alprostadil(0.1-50 ng/ml; 8-26h) causes an upregulation of eNOS and VEGF protein and mRNA expression in HUVEC and decreases HIF-1alpha[4]. Alprostadil (10 ng/mL; 24h) reduces apoptosis and improves the homing of mesenchymal stem cells in pulmonary arterial hypertension by regulating hypoxia-inducible factor 1 alpha[5].
Alprostadil(5 ug/kg; i.p) can reduce pancreatic tissue damage, delay pancreatic cell apoptosis, and reduce inflammation and anti-oxidative stress by inhibiting the JAK2/STAT3 signal pathway, thus protecting the pancreas in acute pancreatitis rat model[6]. Alprostadil (0.3125, 0.625, and 1.25 mg/kg/d; i.p) attenuates AngII-induced cardiac hypertrophy via E-prostanoid (EP) 3 receptor activation and Netrin-1upregulation[7].
References:
[1]. Kiriyama M, Ushikubi F, et,al. Ligand binding specificities of the eight types and subtypes of the mouse prostanoid receptors expressed in Chinese hamster ovary cells. Br J Pharmacol. 1997 Sep;122(2):217-24. doi: 10.1038/sj.bjp.0701367. PMID: 9313928; PMCID: PMC1564924.
[2]. Cattaneo MG, Pola S, et,al. Alprostadil suppresses angiogenesis in vitro and in vivo in the murine Matrigel plug assay. Br J Pharmacol. 2003 Jan;138(2):377-85. doi: 10.1038/sj.bjp.0705051. PMID: 12540529; PMCID: PMC1573673.
[3]. Hauck EW, Altinkilic BM, et,al. Prostaglandin E1 long-term self-injection programme for treatment of erectile dysfunction--a follow-up of at least 5 years. Andrologia. 1999;31 Suppl 1:99-103. doi: 10.1111/j.1439-0272.1999.tb01458.x. PMID: 10643527.
[4]. Haider DG, Bucek RA, et,al. PGE1 analog alprostadil induces VEGF and eNOS expression in endothelial cells. Am J Physiol Heart Circ Physiol. 2005 Nov;289(5):H2066-72. doi: 10.1152/ajpheart.00147.2005. Epub 2005 Jun 10. PMID: 15951350.
[5]. Jiang DT, Tuo L, et,al. Prostaglandin E1 reduces apoptosis and improves the homing of mesenchymal stem cells in pulmonary arterial hypertension by regulating hypoxia-inducible factor 1 alpha. Stem Cell Res Ther. 2022 Jul 16;13(1):316. doi: 10.1186/s13287-022-03011-x. PMID: 35842683; PMCID: PMC9288720.
[6]. Fei S, Li W, et,al. Protective Effect of Alprostadil on Acute Pancreatitis in Rats via Inhibiting Janus Kinase 2 (JAK2)/STAT3 Signal Transduction Pathway. Med Sci Monit. 2019 Oct 13;25:7694-7701. doi: 10.12659/MSM.919148. PMID: 31606729; PMCID: PMC6807527.
[7]. Shen Y, Wang X, et,al. Prostaglandin E1 attenuates AngII-induced cardiac hypertrophy via EP3 receptor activation and Netrin-1upregulation. J Mol Cell Cardiol. 2021 Oct;159:91-104. doi: 10.1016/j.yjmcc.2021.06.009. Epub 2021 Jun 18. PMID: 34147480.
前列地尔Alprostadil作为前列腺素受体配体,对小鼠EP3、EP4、EP2、IP和EP1的结合亲和Kis分别为1.1 nM、2.1 nM、10 nM、33 nM和36 nM。 Alprostadil能够抑制血小板聚集和血栓素A2生成,有利尿和保护肾功能的作用[1-3]。
Alprostadil (0.1-50 ng/ml; 8-26h)引起HUVEC中eNOS和VEGF蛋白及mRNA表达上调,降低HIF-1alpha [4]。Alprostadil (10 ng/mL; 24h)通过调节HIF-1alpha,减少肺动脉高压中细胞凋亡,促进间充质干细胞归巢[5]。
Alprostadil (5 ug/kg; i.p)可通过抑制JAK2/STAT3信号通路,减轻胰腺组织损伤,延缓胰腺细胞凋亡,减轻炎症和抗氧化应激,从而保护急性胰腺炎模型大鼠胰腺[6]。Alprostadil (0.3125, 0.625, and 1.25 mg/kg/d; i.p)通过E-prostanoid (EP) 3受体激活和Netrin -1上调来减轻血管内皮细胞诱导的心肌肥大[7]。