Systematic survery for biologically active peptides in the atrium and pheochromocytoma tissue.

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We discovered adrenomedullin (AM) in 1993 and found another hypetensive peptide proadrenomedullin N-terminal 20 peptide (PAMP) which is produced from adrenomedullin precursor. We have clarified that AM is a new cardiovascular hormone to regulate circulation and body fluid homeostasis. Further, AM shows protective actions for the heart and blood vessels in vitro and in vivo, suggesting that AM may be a new drugs for cardiovascular and inflammatory diseases. Thus, it is important to discover the new hormone and to study its function. We have concurrently advanced the another project to discover still unidentified vasoactive peptide in the porcine atrium and human pheochromocytoma tissue.AM was discovered monitoring the activity that elevate cAMP in the rat platelet. We have searched biological active peptide using the cAMP elevation in cultured cells from pheochromocytoma. Using this assay, we isolated several peptides from pheochromocytoma tissue. These peptide were found to be VIP, PAC … More AP, CGRP and PHM. These peptides were known peptides, but we have isolated novel peptide which exist in the the pheochromocytoma. Many biologically active peptides has C-terminal amide structure which is essential for biological activity. We have established a novel method to detect a peptide with C-terminal amide structure. Using this method, we have isolated a novel 14 amino acids peptide in the atrium whose C-terminus was amidated. This peptide was termed amidicin. Amidicin is widely distributed in porcine tissue and is especially abundant in pituitary gland, cardiac ventricle and spleen. We have developed radioimmunoassay for human amidicin, and examined the distribution of amidicin in human tissue. We found that human amidicin is abundant in human pheochromocytoma tissue. We purified human amidicin from pheochromocytoma and determined its structure. Furthermore, amidicin was found to circulate in human blood in a considerable concentration. Amidicin may be a possible new peptide participating in circulation control. Less