A hypotensive peptide
Proadrenomedullin (N-20) (PAMP-20) is an endogenous peptide with hypotensive activity. It consists of the 20 N-terminal amino acids of proadrenomedullin and is found primarily in human adrenal medulla and pheochromocytoma tissue, with small amounts present in the heart, lung, liver, spleen, pancreas, kidney, small intestine, and cerebral cortex. PAMP-20 is an agonist of the G protein-coupled orphan receptor MRGPRX2 that inhibits forskolin-induced cAMP accumulation in CHO cells expressing the human receptor with an EC50 value of 251 nM. It inhibits catecholamine secretion and sodium and calcium influx induced by the acetylcholine receptor (AChR) agonist carbachol in bovine adrenal medullary cells in vitro (IC50s = 1.6, 2.5, and 1 μM, respectively). PAMP-20 induces a hypotensive response in anesthetized rats when administered at doses of 10, 20, and 50 nmol/kg by intravenous bolus injection. It also dose-dependently reduces systemic arterial and hindlimb perfusion pressure in anesthetized cats when injected intravenously or into the hindlimb perfusion circuit, respectively, indicating vasodilator activity.
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