ENDOTHELIN STIMULATES PHOSPHATIDYLINOSITOL TURNOVER IN RAT RIGHT AND LEFT ATRIA

The effect of endothelin on phosphatidylinositol (PI) turnover has been investigated in isolated rat atria by measuring the generation of inositol phosphates (IPs) following [H-3]inositol phospholipid labelling. In the presence of 10 mM LiCl, endothelin caused dose-dependent increases in the accumulations of inositol mono-, bis- and trisphosphate (IP1, IP2 and IP3) which were maximal at 10(-6) M endothelin. The dose-response relationship was similar in right and left atria, but right atria showed a higher maximal IP response. Endothelin produced a rapid and transient stimulation of IP3 accumulation, which was maximal at 30 s followed by a slower increase which continued linearly past 20 min. During both the initial phase and the sustained phase the only isomer of IP3 present at detectable levels was the 1,4,5-isomer. As with endothelin, responses to noradrenaline also were higher in right atria compared with left atria and showed a biphasic pattern of release of IP3. These data demonstrate that endothelin receptors in rat atria are coupled to stimulation of the PI turnover pathway in an apparently similar manner to alpha-1-adrenoceptors. The PI pathway may be important in mediating the reported cardiac actions of endothelin.