title: Vascular smooth muscle cells metabolize endothelin-1 in the absence of a functional receptor.
abstract: Endothelin-1 (ET-1), a 21 amino acid vasoconstrictor peptide synthesized by vascular endothelial cells, exerts powerful actions on the underlying smooth muscle cells. The receptor and signal transduction mechanisms for ET-1 have been well characterized in rat aortic A10 vascular smooth muscle cells (A10VSMC). This investigation has characterized the internalization and metabolism of [125I]ET-1 by A10VSMC. A10VSMC internalized [125I]ET-1 rapidly in a receptor-mediated manner. However, inhibition of the binding/internalization had no effect on the metabolism of [125I]ET-1 by these cells. Thus, the presence of excess unlabeled ET-1 in the incubation, treatment of the cells with ET receptor antagonists, and homologous ligand-induced down-regulation of the ET-1 receptor all inhibited binding and internalization of [125I]ET-1 by A10VSMC, but not its metabolism. Furthermore, addition of excess unlabeled ET-1 to the incubations containing cells pretreated with the homologous ligand (receptor down-regulated cells) also failed to inhibit the metabolism of [125I]ET-1. Essentially similar characteristics of [125I]ET-1 binding and metabolism were exhibited by primary cultures of smooth muscle cells derived from rat thoracic aorta. Such ability of the vascular smooth muscle cells to degrade ET-1, which is produced constitutively by the endothelial cells, presents a novel mechanism in the regulation of its local and circulating concentration.
mesh_terms: D000818:Animals; D001414:Bacitracin / Q000494:pharmacology; D001692:Biological Transport; D002103:Cadaverine / Q000031:analogs & derivatives / Q000494:pharmacology; D002478:Cells, Cultured; D004705:Endocytosis; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006020:Glycopeptides / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats; D011503:Transglutaminases / Q000037:antagonists & inhibitors
chemical_list: D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D004791:Enzyme Inhibitors; D006020:Glycopeptides; D011480:Protease Inhibitors; D001414:Bacitracin; D011503:Transglutaminases; C008542:monodansylcadaverine; D002103:Cadaverine; C008890:phosphoramidon