Adrenomedullin, a novel vasoactive hormone, binds to mouse astrocytes and stimulates cyclic AMP production

We have examined the effects of adrenomedullin (AM), a novel hypotensive peptide first isolated from human pheochromocytoma, on receptor binding and cyclic AMP (cAMP) generation in primary cultures of mouse astrocytes. Competition binding studies showed that rat adrenomedullin (rAM) displaced the specific binding of [125I]rAM in a dose-dependent manner, with an estimated IC50 of 33 nM. Rat calcitonin gene-related peptide (rCGRP), which interacts with AM receptors in some vascular tissues, did not produce significant displacement of [125I]rAM at concentrations up to 3.3 microM. rAM stimulated cAMP production in mouse astrocytes in a dose-dependent manner, with an EC50 of 74 nM and a maximal stimulatory concentration of 1 microM. CGRP8-37, a CGRP receptor antagonist, failed to inhibit the cAMP response to rAM, although it attenuated CGRP-stimulated cAMP production. These data indicate that cultured mouse astrocytes possess specific AM receptors which are coupled to adenylate cyclase but do not interact with CGRP. AM may function as a neuropeptide and may play a role in the central regulation of blood pressure and body fluid balance.