Bell D, Tamamori M, Marumo F, Hiroe M, McDermott B J, Ito H
Second Department of Internal Medicine, Tokyo Medical and Dental University, Japan.
Regul Pept. 1997 Jul 23;71(1):1-7. doi: 10.1016/s0167-0115(97)01015-x.
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.
我们先前报道过，降钙素基因相关肽（CGRP）在成年大鼠心室体外培养中具有肥大效应，从最广泛的意义上讲，这种效应表现为每个细胞的蛋白质质量增加。本研究的目的是确定该肽是否还能增加新生大鼠心室肥大心肌细胞的表面积，并诱导心房钠尿肽（ANP）和骨骼肌α-肌动蛋白mRNA的表达。与同期在无血清的最低必需培养基（MEM）中培养的细胞相比，在CGRP存在下培养的细胞在48小时后出现了难以察觉的肥大。100 pM和1 nM的CGRP显著增加了细胞表面积，分别比无肽时的值大1.82倍和2.15倍（659.64±23.48平方微米，n = 10）。CGRP1受体的选择性拮抗剂CGRP8-37（200 nM）显著减弱了CGRP（100 pM和1 nM）的作用。CGRP分别导致编码骨骼肌α-肌动蛋白和ANP的mRNA表达显著上调，在12小时后达到最大值，浓度为100 pM时，分别比无肽时的值大约高3.6倍和2.5倍。在CGRP8-37（100 nM）存在的情况下，该肽的这些作用完全被消除。总之，CGRP通过CGRP1受体亚型增加肥大心肌细胞的表面积，并诱导ANP和骨骼肌α-肌动蛋白mRNA的表达。
