Receptor activity-modifying proteins: RAMPing up adrenomedullin signaling.
Adrenomedullin (AM) is a 52-amino-acid multifunctional peptide that circulates in the plasma in the low picomolar range and can exert a multitude of biological effects through an autocrine/paracrine mode of action. The mechanism by which AM transduces its signal represents a novel and pharmacologically tractable paradigm in G protein-coupled receptor signaling. Since its discovery in 1993, the study of AM has emerged into a new field of research with nearly 1800 publications that rivals the renown of other common factors like angiopoetin (1015 publications) and ghrelin (1550 publications). Despite the tremendous strides made in recent years toward unveiling the biochemical and cellular functions of AM, we are still lagging in our understanding of the essential roles of AM in normal and disease physiology. As discussed in this current review, a concerted effort to combine information from clinical, genomic, biochemical, and genetic mouse model sources can provide a focused view to help define the physiological functions of AM. Specifically, we find that certain conditions, such as pregnancy, cardiovascular disease, and sepsis, are associated with robust and dynamic changes in the expression of AM and AM receptor proteins, which together represent an elegant mechanism for altering the physiological responsiveness or function of AM. Thus, the modulation of AM signaling may be further exploited for therapeutic strategies in the management and treatment of human disease.
Gibbons
Carrie
C
Department of Cell and Molecular Physiology, CB # 7545, 6340B MBRB, 103 Mason Farm Road, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599, USA.
Dackor
Ryan
R
Dunworth
William
W
Fritz-Six
Kimberly
K
Caron
Kathleen M
KM
D053607:Adrenomedullin / Q000097:blood / Q000235:genetics / Q000502:physiology*; D000818:Animals; D004194:Disease; D015870:Gene Expression; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D023421:Models, Animal; D058261:Receptor Activity-Modifying Proteins; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction
D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D058261:Receptor Activity-Modifying Proteins; D043562:Receptors, G-Protein-Coupled; D053607:Adrenomedullin