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.