Calcitonin gene-related peptide (CGRP) increases cell surface area and induces expression of skeletal alpha-actin ANP mRNA in hypertrophying neonatal cardiomyocytes

Abstract

We have reported previously that calcitonin gene-related peptide (CGRP) exerts hypertrophic effects, defined in the broadest sense as increased mass of protein per cell, in adult rat ventricular in vitro. The aim of the present investigation was to determine whether the peptide also increases the cell surface area of, and induces expression of ANP and skeletal alpha-actin mRNA in hypertrophying neonatal rat ventricular cardiomyocytes. Cells cultured in the presence of CGRP were invisibly 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 greater, respectively, than in the absence of peptide (659.64 +/-23.48 microns 2, n = 10). The selective antagonist at CGRP1, receptors, CGRP8-37(200nM), significantly attenuated the effects of CGRP (100 pM and 1 nM). CGRP caused a marked up-regulation of the expression of mRNA encoding 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 peptide were completely abolished in the presence of CGRP8-37(100 nM). In conclusion, CGRP increases cell surface area and induces expression of ANP and skeletal alpha-actin mRNA in hypertrophying cardiomyocytes via the CGRP1, receptor subtype.