The Calcium-Sensing Receptor is Upregulated in Post Myocardial Infarct Hearts and Downregulates ANP Expression in Rat Cardiac Myocytes but is Not Expressed in Rat Cardiac Fibroblasts In Vitro

Recently, several reports demonstrated functional expression of calcium-sensing receptor (CaSR) in the heart. Initial reports found the CaSR to be present in the cardiomyocytes, in contrast a recent report have found the CaSR to be present in sheep fibroblasts of the heart. The calcimimetic drug AMG 073 is a pharmacological (allosteric) modulator of CaSR that is in clinical use for the treatment of hyperparathyroidism. Here, we show that CaSR mRNA levels were upregulated in the hearts from rats having myocardial infarction (MI) compared to sham operated rats. Furthermore, we found that in rat cardiomyocytes AMG 073 in the presence of extracellular Ca 2+ decreased mRNA levels of atrial natriuretic pre-pro peptide (pre-pro-ANP), which is a marker for cardiac hypertrophy. Surprisingly, CaSR mRNA was not detectable in rat neonatal ventricular fibroblasts (RNVF) by reverse transcriptase PCR. Yet, extracellular calcium exerts a biphasic response in DNA synthesis of RNVFs and AMG 073 seems to suppress DNA synthesis in RNVFs. In addition, calcium and calcimimetic activate MEK/ERK signalling in RNVFs that appears to be independent of CaSR activation. From these results it appears that an additional calcium-sensing mechanism may exist in RNVF. Our findings may be of importance in regards to a potential protective role of calcium and perhaps CaSR against cardiac hypertrophy.