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The ability of endothelin to stimulate phosphatidylinositol hydrolysis in rings of rat aorta was studied. Endothelin 10-8-10-5 mol/l caused increases of 200–1000% in inositol phosphate levels. However, physiological responses to endothelin have been reported in the concentration range 10-10-10-8 mol/l. Thus phosphatidylinositol hydrolysis as measured in the present study does not correlate directly with functional responses. Phosphatidylinositol hydrolysis in response to endothelin was attenuated but not abolished by removal of endothelium. Attenuation of inositol phosphate production was also observed with time, consistent with the hypothesis that continuous exposure to the agonist can cause desensitization of the endothelin receptor.