OPENING LECTURE: PDF OnlyProduction of Endothelin by Vascular Smooth Muscle CellsKanse, S. M.; Takahashi, K.; Warren, J. B.*; Perera, T.†; Porta, M.‡; Ghatei, M.; Bloom, S. R. Author Information *Departments of Endocrinology, Clinical Pharmacology †Histopalhology‡, and ‡iabetic Retinopathy, Royal Postgraduate Medical School, London, U.K. Journal of Cardiovascular Pharmacology: Volume 17 - Issue - p S113-116 Free Abstract Summary Endothelin (ET) production by cultured vascular smooth muscle cells isolated from rat and rabbit aortae was measured by a specific radioimmunoassay. Vascular smooth muscle cells released ET at a rate of 0.6 (range of 0.1–1) fmol/IO5 cells/24 h compared to 45 (range of 10–80) fmol/105 cells/h for endothelial cells. ET immunoreactivity was confirmed as ET-1 by fast protein liquid chromatography. Calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) suppressed basal release of ET by 24–66% from both rat and rabbit vascular smooth muscle. Forskolin and dibutryl-cAMP similarly suppressed ET release by 33–86%, suggesting that increased intracellular cAMP may account for the mechanism of action of CGRP and VIP. In contrast. CGRP and VIP did not have any effect on ET release from endothelial cells. The characteristics and regulation of ET binding sites on vascular smooth muscle cells were measured using [I25I]ET-1 as the radioligand. Pretreatment with CGRP, VIP. forskolin, and dibutryl-cAMP increased the ET receptor density on both smooth muscle cell types. The low level production of ET-1 by vascular smooth muscle cells may have an important autocrine function and may be under regulation of neuropeptides localized to perivascular nerves. © Lippincott-Raven Publishers.