Grześk Elżbieta, Szadujkis-Szadurska Katarzyna, Wiciński Michał, Malinowski Bartosz, Sinjab Thabit A, Tejza Barbara, Pujanek Maciej, Janiszewska Ewa, Kopczyńska Anna, Grześk Grzegorz
Department of Pediatrics, Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University, 85-094 Bydgoszcz, Poland.
Department of Pharmacology and Therapeutics, Faculty of Medicine, Collegium Medicum, Nicolaus Copernicus University, 85-094 Bydgoszcz, Poland.
Biomed Rep. 2016 Jan;4(1):117-121. doi: 10.3892/br.2015.543. Epub 2015 Nov 10.
2,4,6-Trimethyl--[3-(trifluoromethyl)phenyl]benzenesulfonamide (m-3M3FBS) activates phospholipase C and stimulates apoptosis; however, in smooth muscle cells it may increase the perfusion pressure. The main aim of the present study was to evaluate the physiological effect of direct stimulation of phospholipase C on vascular smooth muscle reactivity using three contraction models. Experiments were performed on the isolated and perfused tail artery of Wistar rats. The contraction force in the present model was measured by an increased level of perfusion pressure with a constant flow. Concentration-response curves (CRCs) obtained for phenylephrine, arg-vasopressin, mastoparan-7 and Bay K8644 presented a sigmoidal association. In comparison to the control curves, CRCs in the presence of m-3M3FBS were significantly shifted to the left except for Bay K8644. Analyses of calcium influx suggest that in the presence of m-3M3FBS the calcium influx from intra- and extracellular calcium stores was significantly higher. The results of the present experiments suggest that m-3M3FBS significantly increases the reactivity of vascular smooth muscle stimulated with metabotropic receptors or G-protein by an increase in calcium influx from intra- and extracellular calcium stores. The current knowledge regarding the apoptotic pathway shows the significance of calcium ions involved in this process, thus, m-3M3FBS may induce apoptosis by an increase of cytoplasmic calcium concentration; however, simultaneously, the use of this mechanism in therapy must be preceded by a molecular modification that eliminates a possible vasoconstriction effect.
2,4,6-三甲基- -[3-(三氟甲基)苯基]苯磺酰胺（间-3M3FBS）可激活磷脂酶C并刺激细胞凋亡；然而，在平滑肌细胞中它可能会增加灌注压力。本研究的主要目的是使用三种收缩模型评估直接刺激磷脂酶C对血管平滑肌反应性的生理影响。实验在Wistar大鼠分离并灌注的尾动脉上进行。在本模型中，收缩力通过在恒定流量下灌注压力水平的升高来测量。去氧肾上腺素、精氨酸加压素、马斯托帕兰-7和Bay K8644的浓度-反应曲线（CRCs）呈现出S形关联。与对照曲线相比，除Bay K8644外，在间-3M3FBS存在下的CRCs显著向左移动。钙内流分析表明，在间-3M3FBS存在下，来自细胞内和细胞外钙库的钙内流显著更高。本实验结果表明，间-3M3FBS通过增加来自细胞内和细胞外钙库的钙内流，显著增加了由代谢型受体或G蛋白刺激的血管平滑肌的反应性。目前关于凋亡途径的知识表明钙离子在这一过程中的重要性，因此，间-3M3FBS可能通过增加细胞质钙浓度来诱导细胞凋亡；然而，同时，在治疗中使用这种机制之前必须进行分子修饰，以消除可能的血管收缩作用。
