| Research Abstract |
(1) By using gene expression system, we checked ligand selectivity and cGMP production of rat and human GC-A and GC-B receptors. Both atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) are ligands specific to GC-A receptor, while C-type natriuretic peptide (CNP) to GC-B receptor. In rat GC-B receptor, we found non-functional receptor with binding activity. Furthermore, natriuretic peptides were shown to inhibit growth of cultured vascular smooth muscle cells as well as GC-B-expressing CHO cells.
(2) CNP has been recognized as a neuropeptide functioning in the central nervous system. By using the PCR and RIA methods, we found CNP and its mRNA in the peripheral tissue. Furthermore, significant production of CNP was detected in monocytic leukemia cell line (THP-1), when stimulated with TPA and differetiated into macrophage-like cells. These results suggest that CNP is a local regulator functioning through paracrine mode, especially in the region of arteriosclerosis or vascular injury.
(3) ANP and BNP bind to GC-A receptor and function as circulating hormones. To elucidate their functional differences, we measured peptide concentration and mRNA levels. In patients with heart failure, plasma BNP concentration increases more than 100-fold, while that of BNP decreases to less than 10% in water-deprived rats. These results suggest that BNP is an emergency hormone supporting and reinforcing the function of ANP.
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