Endothelin, a vasoconstrictor peptide, plays important roles not only in the mammalian circulatory system but also in non-mammalian systems, such as the gill lamellar vascular network with complex structural characteristics. Here, we show that (i) the contraction of pillar cells that delimit the lamellar vasculature is controlled by endothelin through the type A endothelin receptor (ETA) linked to the intracellular calcium signaling system and (ii) ETA receptor is also highly expressed on fugu erythrocytes, a hitherto unexpected finding. Database mining revealed the presence of five endothelin receptor (ETR) sequences in the fugu genome. By Northern blotting, cDNA cloning, and fura-2 monitoring, the branchial ETR subtype was shown to be ETA able to induce a Ca2+ transit. Immunohistochemistry revealed its pillar cell and erythrocyte localization. These results suggest an endothelin/ETA-Mediated coordinated regulation of the pillar cell shape and erythrocyte membrane flexibility. (c) 2007 Elsevier Inc. All rights reserved.