The purpose of the present study was to determine if cardiac myocytes and nonmyocytes secrete adrenomedullin, to investigate the effects of adrenomedullin on cAMP and cGMP levels in cardiac myocytes and nonmyocytes, to study the effect of calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8-37) and adrenomedullin-specific receptor antagonist, adrenomedullin-(22-52) on response to adrenomedullin and CGRP. Neonatal (days 1-2) cardiac myocytes and nonmyocytes were prepared from the ventricle of Wistar rats. Not only cardiac myocytes, but also nonmyocytes secrete almost equal amounts of adrenomedullin into the media. Both adrenomedullin and CGRP increased the cAMP levels, not the cGMP levels, both in the myocytes and nonmyocytes. In myocytes, CGRP-(8-37), almost completely inhibited the adrenomedullin- and CGRP-induced cAMP formation. In nonmyocytes, CGRP-(8-37) completely inhibited the cAMP levels induced by adrenomedullin and CGRP. More profound antagonistic effect of CGRP-(8-37) on cAMP levels induced by adrenomedullin was observed in nonmyocytes than in myocytes. In contrast, antagonistic effect of adrenomedullin-(22-52) for adrenomedullin-stimulated cAMP formation was considerably less potent than CGRP-(8-37) both in myocytes and nonmyocytes. Adrenomedullin-(22-52) did not affect the cAMP formation induced by CGRP either in myocytes or nonmyocytes. These results suggest that myocytes and nonmyocytes secrete adrenomedullin and that adrenomedullin increases cAMP levels possibly via different receptors in myocytes and nonmyocytes.