Evidence that endothelin-1 (ET-1) inhibits insulin-stimulated glucose uptake in rat adipocytes mainly through ETA receptors

The specificity of endothelin (ET) receptors involved in the inhibition of insulin-stimulated glucose uptake ([SGU) in rat adipocytes was investigated . Adipocytes were isolated from the epididymal fat pads of Sprague-Dawley r ats. To determine receptor subtypes, we used three ET isopeptides, ET-1 and ET-2, both of which are nonselective agonists, and ET-3, a selective agoni st for ETc receptors, to displace [I-125]]ET-1 binding from the fat cells. The efficiency of displacement was ET-1 > ET-2 much greater than ET-3, indi cating that the primary receptors involved belonged to the ETA subtype. At an equal concentration of 1 mu mol/L, BQ-610, a selective ETA antagonist, d isplaced [I-125]ET-1 from binding to far cells, whereas IRL-1038, a selecti ve ETB antagonist, did not. Using [H-3]2-deoxy-D-1-glucose ([H-3]2-DG) as a tracer in studies of glucose uptake, we found that equimolar BQ-610 comple tely reversed the inhibitory effect of ET-1 on ISGU, whereas IRL-1038 was i neffective. Northern blot analysis of adipocyte receptors showed abundant m RNA for ETA, but no ETB subtype. These results clearly demonstrate that ETA is the predominant receptor in rat adipocytes. Copyright (C) 1998 by W.B. Saunders Company.