CALCITONIN-GENE-RELATED PEPTIDE (CGRP) INCREASES CELL-SURFACE AREA AND INDUCES EXPRESSION OF SKELETAL ALPHA-ACTIN AND ANP MESSENGER-RNA IN HYPERTROPHYING NEONATAL CARDIOMYOCYTES

We have reported previously that calcitonin gene-related peptide (CGRP ) exerts hypertrophic effects, defined in the broadest sense as increa sed mass of protein per cell, in adult rat ventricular cardiomyocytes in vitro. The aim of the present investigation was to determine whethe r the peptide also increases the cell surface area of, and induces exp ression of ANP and skeletal alpha-actin mRNA in hypertrophying neonata l rat ventricular cardiomyocytes. Cells cultured in the presence of CG RP were visibly hypertrophied after 48 h compared to cells cultured in serum-free MEM for the same period. CGRP, 100 pM and 1 nM, increased cell surface area significantly and to values 1.82- and 2.15-fold grea ter, respectively, than in the absence of peptide (659.64+/-23.48 mu m (2), n = 10). The selective antagonist at CGRP(1), receptors, CGRP(8-3 7) (200 nM), significantly attenuated the effects of CGRP (100 pM and 1 nM). CGRP caused a marked up-regulation of the expression of mRNA en coding skeletal alpha-actin and ANP, respectively, maximally after 12 h and at a concentration of 100 pM, to values approximately 3.6- and 2 .5-fold greater than in the absence of peptide. These effects of the p eptide were completely abolished in the presence of CGRP(8-37) (100 nM ). In conclusion, CGRP increases cell surface area and induces express ion of ANP and skeletal alpha-actin mRNA in hypertrophying cardiomyocy tes via the CGRP(1), receptor subtype. (C) 1997 Elsevier Science B.V.