ADRENOMEDULLIN, A NOVEL VASOACTIVE HORMONE, BINDS TO MOUSE ASTROCYTESAND STIMULATES CYCLIC-AMP PRODUCTION

We have examined the effects of adrenomedullin (AM), a novel hypotensi ve peptide first isolated from human pheochromocytoma, on receptor bin ding and cyclic AMP (cAMP) generation in primary cultures of mouse ast rocytes, Competition binding studies showed that rat adrenomedullin (r AM) displaced the specific binding of [I-125]rAM in a dose-dependent m anner, with an estimated IC50 of 33 nM, Rat calcitonin gene-related pe ptide (rCGRP), which interacts with AM receptors in some vascular tiss ues, did not produce significant displacement of [I-125]rAM at con cen trations up to 3.3 mu M. rAM stimulated cAMP production in mouse astro cytes in a dose-dependent manner, with an EC(50) of 74 nM and a maxima l stimulatory concentration of 1 mu M. CGRP(8-37) a CGRP receptor anta gonist, failed to inhibit the cAMP response to rAM, although it attenu ated CGRP-stimulated cAMP production, These data indicate that culture d 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 pr essure and body fluid balance. (C) 1996 Wiley-Liss, Inc.