Structure-activity relationships of adrenomedullin in the circulation and adrenal gland.
Adrenomedullin (ADM) is a recently discovered vasoactive peptide that has potent vasodilator activity in the pulmonary and peripheral vascular beds and has significant effects on endocrine function. ADM is a member of the CGRP/amylin superfamily of peptides based largely on the presence of the six-membered ring structure and C-terminal amidation that is highly conserved in this family. Proadrenomedullin is a 185 amino acid precursor with enzymatic cleavage sites for both ADM and a unique 20 amino acid peptide named proadrenomedullin N-terminal 20 peptide (PAMP). ADM and PAMP are found in a variety of organ systems, and plasma levels of the peptides are increased in pathophysiologic conditions. Both peptides have hypotensive and vasodilator activity in the pulmonary and regional vascular beds and have significant effects on the endocrine system, including the adrenal gland. ADM (15-52), which retains the six-membered ring structure, maintains the vasodilator activity of ADM, suggesting that the 14 amino acid N-terminal extension is not necessary for the full agonist activity. However, analogs, such as ADM-(22-52) and ADM-(40-52), which do not contain the six-member ring structure, lack agonist activity. Unlike the full-sequence peptide, hADM-(15-22) and ADM-(16-21), which contain the ring structure, increase systemic arterial pressure in the rat but not in the cat. The present review discusses the structure-activity relationship for the actions of ADM and related peptides and discusses the mechanisms which mediate responses to these widely distributed peptides.
Champion
H C
HC
Department of Pharmacology, Tulane University School of Medicine, New Orleans, LA 70112, USA.
Nussdorfer
G G
GG
Kadowitz
P J
PJ
D000311:Adrenal Glands / Q000502:physiology*; D053607:Adrenomedullin; D000595:Amino Acid Sequence; D000818:Animals; D002415:Cats; D006801:Humans; D008969:Molecular Sequence Data; D010455:Peptides / Q000378:metabolism*; D051381:Rats; D013329:Structure-Activity Relationship; D014665:Vasodilator Agents / Q000378:metabolism*
D010455:Peptides; D014665:Vasodilator Agents; D053607:Adrenomedullin