Endothelin Stimulates Inositol Phosphate Accumulation in Rat Right and Left Atria: A Comparison With Noradrenaline

Abstract

1. The effect of endothelin on phosphatidylinositol turnover in rat atria was investigated by measuring the generation of inositol phosphates following [3H]-inositol labelling. 2. In the presence of 10 mmol/L LiCl, endothelin caused dose-dependent increases in the accumulation of inositol mono, bis and trisphosphates which were maximal at 10(-6) mol/L endothelin. The dose-response relationship was similar in right and left atria, but right atria showed a higher maximal inositol phosphate response. 3. Endothelin produced a rapid and transient stimulation of inositol trisphosphate accumulation, which peaked at 15 s followed by a slower increase which continued linearly past 20 min. 4. The time course of inositol trisphosphate release under noradrenaline stimulation showed a similar profile but the maximum stimulation was smaller than endothelin. 5. As with endothelin, responses to noradrenaline also were higher in right atria compared with left atria. 6. These data demonstrate that endothelin receptors in rat atria are coupled to the stimulation of the phosphatidylinositol turnover pathway in an essentially similar manner to alpha 1-adrenoceptors. The phosphatidylinositol pathway may be important in mediating the reported cardiac actions of endothelin.

A comparative study of endothelin- and platelet-activating-factor-mediated signal transduction and prostaglandin synthesis in rat Kupffer cells

“…ET-3-induced metabolism of phosphoinositides: dose-response relationship and Ca2' requirement ET has been shown to stimulate the hydrolysis of phosphoinositides, intracellular Ca2+ mobilization and the influx of extracellular Ca2l in various cells and tissues (Marsden et al, 1989;Takuwa et al, 1989a,b;Kuraja & Woodcock, 1990;Resink et al, 1990;Lin et at., 1990;Vigne et al, 1990). Fig.…”