| Research Abstract |
"Adrenomedullin (AM)" is a novel hypotensive peptide which was discovered in human pheochromocytoma by monitoring the elevating activity of platelet cAMP. In addition, a novel 20 residues hypotensive peptide, termed "proadrenomedullin N-terminal 20 peptide" (PAMP), is processed from proadrenomedullin. In this study , we performed the following study to elucidate biosynthesis and physiological role of PAMP.
(1) We have established highly sensitive enzyme immunoassay for PAMP and PAMP-gly, intermediate form. PAMP as well as AM was widely distributed in human and rat tissue. Especially, PAMP is abundant in mucosal cells in gastrointestinal tract and function as the antimicrobial peptide. Further, we isolated and determined PAMP (9-20) as an endogenous peptide which shows similar biological effect with PAMP.
(2) PAMP receptors are widely distributed in various tissues, among which adrenal glomerulosa and human adrenal adenoma have the most abundant sites. Therefore, we constructed expression cDNA library and investigated the PAMP receptor.
(3) Using an assay system for binding assay for PAMP receptor, we found the peptide which inhibit PAMP to bind its receptor. This peptide consists of 21 amino acids and was termed PAMP Receptor Binding Peptide (PRBP) .
(4) We have succeeded that PAMP transgenic rat and are now studying its phenotype.
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