RECEPTORS FOR THE VASODILATOR MAXADILAN ARE EXPRESSED ON SELECTED NEURAL CREST AND SMOOTH MUSCLE-DERIVED CELLS

Maxadilan is a potent vasodilator peptide isolated from salivary gland s of the blood feeding sand fly Lutzomyia longipalpis. The peptide rel axes rabbit aortic rings in an endothelium independent manner while el evating levels of cAMP and has been found to bind to membrane homogena tes from brain, These studies on tissues have now been expanded with a n examination of binding and signaling of maxadilan to a number of est ablished cell lines and primary cultures, The data reveal that maxadil an binds to and stimulates the accumulation of cAMP in the rat pheochr omocytoma line PC12 and the human neuroblastoma line NBfl. Accumulatio n of cAMP occurred in a transformed mouse pancreatic smooth muscle lin e (MILE) and primary rabbit aorta smooth muscle cells, The peptide did not bind to or induce cAMP formation in the rat thoracic aorta line L 6. Scatchard analysis of binding to the PC12 and NBfl lines indicates that maxadilan binds to a single class of high-affinity receptors. Sim ilar pharmacologic actions and possible structural homologies between maxadilan and calcitonin gene-related peptide (CGRP) suggested the pos sibility that they shared receptors. However, competition studies and comparative second messenger analysis reveal that maxadilan does not i nteract with receptors for CGRP, amylin or adrenomedullin and suggest that this peptide may bind to a novel receptor whose endogenous ligand remains unknown. Copyright (C) 1997 Elsevier Science Ltd.