title: Effect of 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzene-sulfonamide on calcium influx in three contraction models.
abstract: 2,4,6-Trimethyl-N-[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.
authors: Department of Pediatrics, Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University, 85-094 Bydgoszcz, Poland.
authors: Elżbieta
authors: E
authors: Grześk
authors: Department of Pharmacology and Therapeutics, Faculty of Medicine, Collegium Medicum, Nicolaus Copernicus University, 85-094 Bydgoszcz, Poland.
authors: Katarzyna
authors: K
authors: Szadujkis-Szadurska
authors: Department of Pharmacology and Therapeutics, Faculty of Medicine, Collegium Medicum, Nicolaus Copernicus University, 85-094 Bydgoszcz, Poland.
authors: Michał
authors: M
authors: Wiciński
authors: Department of Pharmacology and Therapeutics, Faculty of Medicine, Collegium Medicum, Nicolaus Copernicus University, 85-094 Bydgoszcz, Poland.
authors: Bartosz
authors: B
authors: Malinowski
authors: Department of Pharmacology and Therapeutics, Faculty of Medicine, Collegium Medicum, Nicolaus Copernicus University, 85-094 Bydgoszcz, Poland.
authors: Thabit A
authors: TA
authors: Sinjab
authors: Department of Pediatrics, Hematology and Oncology, Collegium Medicum, Nicolaus Copernicus University, 85-094 Bydgoszcz, Poland.
authors: Barbara
authors: B
authors: Tejza
authors: Department of Pharmacology and Therapeutics, Faculty of Medicine, Collegium Medicum, Nicolaus Copernicus University, 85-094 Bydgoszcz, Poland.
authors: Maciej
authors: M
authors: Pujanek
authors: Department of Pharmacology and Therapeutics, Faculty of Medicine, Collegium Medicum, Nicolaus Copernicus University, 85-094 Bydgoszcz, Poland.
authors: Ewa
authors: E
authors: Janiszewska
authors: Department of Pharmacology and Therapeutics, Faculty of Medicine, Collegium Medicum, Nicolaus Copernicus University, 85-094 Bydgoszcz, Poland.
authors: Anna
authors: A
authors: Kopczyńska
authors: Department of Pharmacology and Therapeutics, Faculty of Medicine, Collegium Medicum, Nicolaus Copernicus University, 85-094 Bydgoszcz, Poland.
authors: Grzegorz
authors: G
authors: Grześk
keywords: 2,4,6-trimethyl-N-[3-(trifluoromethyl)phenyl]benzenesulfonamide; mastoparan-7; phenylephrine; phospholipase C; vasopressin