ADRENOMEDULLIN (RAT)

Description

AM is a potent hypotensive peptide synthesized in the vasculature and various tissues. It is a promising drug target for hypertension and cardiac diseases. AM was isolated and identified from human pheochromocytoma tissue in 1993 by monitoring the activity the elevating intracellular cAMP in rat platelets.

Structure and conformation

Human preproAM consists of 185 aa residues and contains a 21-aa residue signal peptide. AM shares the structural homology of an intramolecular ring structure and has C-terminal amidation with the calcitonin gene-related peptide (CGRP) and amylin. Therefore, AM is considered to be a member of the CGRP family. The sequence identities between AM and other members are not high, including 20% in humans. ProAM includes a unique sequence of 20 aa residues followed by a typical amidation signal, Gly-Lys-Arg. This peptide with an amidated C-terminus is termed proadrenomedullin N-terminal 20 peptide (PAMP). AM is conserved among various vertebrate species, including teleost fish, though the sequence identities are low among species. The sequence of the disulfide ring region and the following C-terminal region are highly conserved in tetrapods, but they vary in teleost fish. Teleost fish possess two types of paralogous am genes: am1 and am4. A mature human AM consists of 52 aa residues and contains a ring structure formed by the intramolecular disulfide bond between cysteine-16 and cysteine-21. The tyrosine residue of the carboxyl end is amidated according to the subsequent amidation signal.