proadrenomedullin , human

Proadrenomedullin (45-92), human, a mid-regional fragment of proadrenomedullin (MR-proADM), consists of amino acids 45–92 of pre-proADM.

Endogenous peptide agonist of Mas related GPR X2 (MRGPRX2, EC50 = 251 nM). Also a noncompetitive nicotinic cholinergic antagonist. Inhibits nicotine-stimulated catecholamine secretion from PC12 cells in vitro, and from sympathetic nerve endings and adrena

Pro-Adrenomedullin(153-185),human, (C143H224N42O43), a peptide with the sequence H2N-SLPEAGPGRTLVSSKPQAHGAPAPPSGSAPHFL-OH, MW= 3219.6. Adrenomedullin (AM) is a ubiquitously expressed peptide initially isolated from phaechromyctoma in 19931. AM was initially identified as a vasodilator, some have cited this as the most potent endogenous vasodilatory peptide found in the body2. Differences in opinion regarding the ability of AM to relax vascular tone arises from the differences in the model system used3. Other effects of AM include increasing the tolerance of cells to oxidative stress and hypoxic injury and angiogenesis. AM is seen as a positive influence in diseases such as hypertension, myocardial infarction, chronic obstructive pulmonary disease and other cardiovascular diseases, whereas it can be seen as a negative factor in potentiating the potential of cancerous cells to extend their blood supply and cause cell proliferation.

Proadrenomedullin N-terminal 12 peptide (PAMP-12), an endogenous fragment originating from the adrenal medulla and spanning amino acids 9-20 of human PAMP-20, plays a role in causing hypotension. It functions as an agonist for the MAS-related G protein-coupled receptor family member X2 (MRGPRX2), inhibiting forskolin-stimulated cAMP accumulation in CHO cells expressing human MRGPRX2 (EC50 = 57.2 nM) and selectively prompting calcium mobilization in these cells (EC50 = 41 nM), but not in cells expressing MRGPRX1, MRGPRX3, or MRGPRX4 at 1 µM. As an antagonist of nicotinic acetylcholine receptors (nAChRs), PAMP-12 obstructs carbachol-triggered catecholamine release and the influx of calcium and sodium (IC50s = 1.3, 0.39, and 0.87 µM, respectively) in primary bovine adrenal chromaffin cells, with no effect on histamine-induced responses (IC50s = >1 µM for all). Additionally, it decreases mean arterial blood pressure in normotensive rats at doses ranging from 10 to 50 nmol/kg.