NDLI: LY-294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one] affects calcium signaling in airway smooth muscle cells independently of phosphoinositide 3-kinase inhibition.

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LY-294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one] affects calcium signaling in airway smooth muscle cells independently of phosphoinositide 3-kinase inhibition.

Content Provider	Semantic Scholar
Author	Tolloczko, Barbara Turkewitsch, Petra Al-Chalabi, Mustafa Martin, James
Copyright Year	2004
Abstract	Phosphoinositide 3-kinase (PI3K) may potentially influence intracellular [Ca(2+)](i) concentration by several mechanisms. We have investigated the effects of phosphoinositide 3-kinase (PI3K) inhibitors wortmannin and LY-294002 [2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one] on Ca(2+) signaling in rat airway smooth muscle (ASM) cells using fura-2 and imaging methodology. Wortmannin (1 microM) and LY-294002 (1 and 10 microM) had opposite effects: wortmannin caused a small increase, whereas LY-294002 caused a significant decrease of peak Ca(2+) responses to serotonin (5-HT). LY-294002 (10 microM) diminished 5-HT-induced ASM cell contraction, measured as a change in cell surface area, and inositol phosphate formation, measured by anion exchange chromatography. Thin layer chromatography revealed that the levels of phospholipase C (PLC) substrate phosphatidylinositol 4,5-bisphosphate were not affected. SDS polyacrylamide gel electrophoresis and Western blotting have shown that both wortmannin and LY-294002 inhibited platelet-derived growth factor-induced PI3K activation. However, PI3K activation could not be detected after 5-HT stimulation. The specific casein kinase-2 (CK2) inhibitor 5,6-dichloro-1-beta-d-ribofuranosyl-benzimidazole (10-40 microM) reduced 5-HT-triggered responses to a similar extent as LY-294002. We conclude that LY-294002 modulates Ca(2+) signaling in rat ASM independently of its action on PI3K by acting on, or upstream of, PLC, possibly by inhibiting CK2.
Starting Page	93
Ending Page	96
Page Count	4
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://jpet.aspetjournals.org/content/jpet/311/2/787.full.pdf
PubMed reference number	15194708v1
Volume Number	311
Issue Number	2
Journal	The Journal of pharmacology and experimental therapeutics
Language	English
Access Restriction	Open
Subject Keyword	1-Phosphatidylinositol 3-Kinase 1-Phosphatidylinositol-4,5-bisphosphate phosphodiesterase 2-Pyridinylmethylsulfinylbenzimidazoles Anions Benzimidazoles Blood Platelets Calcium Signaling Casein Kinase II Fura-2 Gel Electrophoresis (lab technique) Hippocampus (Brain) Inositol Phosphates LY 294002 Phosphatidylinositol 4,5-Diphosphate Phosphatidylinositols Phospholipase C Platelet-Derived Growth Factor Polyacrylamide Gel Electrophoresis Serotonin Smooth muscle (tissue) Thin Layer Chromatography Western Blotting inorganic phosphate inositol phosphate biosynthetic process polyacrylamide gels wortmannin
Content Type	Text
Resource Type	Article

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