Brain natriuretic peptide (BNP) was first isolated from porcine brain and then was shown to present mainly in the heart. To characterize the processing pathways and secretion mechanism of BNP, molecular forms of BNP in the heart and plasma were determined.
In the case of rat, two molecular forms of BNP, gamma-BNP and BNP-45, were identified in the cardiac atrium and ventricle, where ANP is stored only as gamma-ANP. In the ventricle, gamma-BNP was a major molecular form, while BNP-45 was in the atrium. Only BNP-45 was observed in the blood stream, where ANP circulates as alpha-ANP. In human, BNP was also present as two molecular forms gamma-BNP and BNP-32. A major molecular form of human BNP was BNP-32 in the atrium and gamma-BNP in the ventricle. On the other hand, in addition to BNP-32, gamma-BNP was also identified in human plasma and gamma-BNP was present as a major molecular form in healthy subjects. This is in sharp contrast to alpha-ANP in human plasma. These data indicate that bi
osynthesis, proteolytic processing and secretion systems of BNP are different from those of ANP. These differences may reflect the characteristic mRNA structure and species differences in the amino acid sequences of BNP precursors.
Our recent identification of the third natriuretic peptide ; C-type natriuretic peptide (CNP) has revealed that the natriuretic peptide family consists of ANP, BNP and CNP. To clarify the processing pathways of the natriuretic peptide family, we determined the regional distribution and the endogenous molecular forms of CNP.
In porcine brain, tissue concentration of CNP was the highest in the three natriuretic peptides at about 0.79 pmol/g wet wt., which was slightly higher than that of BNP and about 10 times higher than that of ANP. In human brain, CNP was detected at a concentration of 1.04 pmol/g wet wt., being about 25 times or 70 times higher than ANP or BNP. In contrast, a significant concentration of CNP was not detected in peripheral tissues, including heart. Only in adrenal medulla, CNP was found at a concentration of 0.7 pmol/g wet wt., as it does in the case of ANP and BNP. In the central nervous system, CNP was present mainly as CNP-53 and CNP-22 and concentration of CNP-53 was found about 10 times higher than that of CNP-22. These results indicate that CNP is localized in the central nervous system and its expresion and processing patterns are regulated bydifferent mechanisms from those of ANP and BNP.
The present study shows that CNP functions as a neuropeptide in the central nervous systems, whereas ANP and BNP function as hormones in the circulating system. Less