Positive inotropy mediated via CGRP receptors in isolated human myocardialtrabeculae

Isometric contractile force were studied on isolated human myocardial trabe culae that were paced at 1.0 Hz in tissue baths. Alpha calcitonin gene-rela ted peptide (alpha-CGRP) had a potent positive inotropic effect in most tra beculae from both the right atrium and left ventricle, and this effect was partially antagonized by the CGRP(1) receptor antagonist alpha-CGRP-(8-37) (10(-6) M). Amylin and the CGRP(2) receptor agonist [Cys(acetylmethoxy)(2.7 )]CGRP had a positive inotropic effect in some trabeculae, whereas adrenome dullin had no inotropic effect. Using reverse transcriptase-polymerase chai n reaction (PCR) mRNAs encoding the human calcitonin receptor-like receptor and the receptor associated modifying proteins (RAMPs) RAMP1, RAMP2, and R AMP3 were detected in human myocardial trabeculae from both the right atriu m and left ventricle. In conclusion, functional CGRP(1) and CGRP(2) recepto rs may mediate a positive inotropic effect at both the atrial and ventricul ar level of the human heart, mRNAs for calcitonin receptor-like receptor an d specific RAMPs further support the presence of CGRP receptors. (C) 2000 E lsevier Science B.V. All rights reserved.