inosine-triphosphate and flosequinan

In rat aorta endothelin-1 (10(-8) M) induces significant increases in inositol 1,4,5-trisphosphate (IP3) levels after a 30 s exposure. An increase in particulate protein kinase C activity is also observed at 30 s with a second peak of activity occurring after 10 min. Flosequinan, at concentrations of 10(-6) M or greater, inhibits these endothelin-1-induced changes in both IP3 and particulate protein kinase C activity in the absence of changes in either cyclic GMP or cyclic AMP. It is likely therefore that flosequinan inhibits the transduction mechanisms between the endothelin-1 receptor and hydrolysis of phosphatidylinositol 4,5-bisphosphate, possibly at the level of a G-protein. These results provide a mechanism to explain the vasodilator effects of flosequinan observed in vitro.

Topics: Animals; Aorta, Thoracic; Cyclic AMP; Cyclic GMP; Cytosol; Endothelins; In Vitro Techniques; Inosine Triphosphate; Male; Muscle Proteins; Protein Kinase C; Quinolines; Rats; Rats, Wistar; Vasodilator Agents