Homologous desensitization of the effects of endothelin on rabbit aorta rings and on cultured rat aorta smooth muscle cells

The effects of endothelin-1 on normal and everted rabbit aorta rings and on cultured rat aortic smooth muscle cells were studied. Endothelin-1 (40 nM) contracted both normal and everted rings, and was still able to induce a prolonged contraction in Ca2(+)-free medium. Treatment of cultured cells with 100 nM endothelin-1 caused a sharp transient increase in 45Ca2+ efflux. The contractile and 45Ca2+ responses showed severe and specific desensitization towards endothelin-1; the responses to angiotensin II and adrenaline were not affected. The contractile responses to endothelin-1 were not affected by previous treatment with angiotensin II or with the angiotensin receptor antagonist, [Sar1,Ala8]angiotensin II. It is concluded that endothelin-1 acts on its own specific receptors to elicit Ca2+ mobilization from both intracellular and extracellular sources.