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 glands of the blood feeding sand fly Lutzomyia longipalpis. The peptide relaxes rabbit aortic rings in an endothelium independent manner while elevating levels of cAMP and has been found to bind to membrane homogenates from brain. These studies on tissues have now been expanded with an examination of binding and signaling of maxadilan to a number of established cell lines and primary cultures. The data reveal that maxadilan binds to and stimulates the accumulation of cAMP in the rat pheochromocytoma line PC12 and the human neuroblastoma line NBfl. Accumulation of cAMP occurred in a transformed mouse pancreatic smooth muscle line (MILE) and primary rabbit aorta smooth muscle cells. The peptide did not bind to or induce cAMP formation in the rat thoracic aorta line L6. Scatchard analysis of binding to the PC12 and NBfl lines indicates that maxadilan binds to a single class of high-affinity receptors. Similar pharmacologic actions and possible structural homologies between maxadilan and calcitonin gene-related peptide (CGRP) suggested the possibility that they shared receptors. However, competition studies and comparative second messenger analysis reveal that maxadilan does not interact with receptors for CGRP, amylin or adrenomedullin and suggest that this peptide may bind to a novel receptor whose endogenous ligand remains unknown.