Proadrenomedullin N-terminal 20 peptide: minimal active region to regulate nicotinic receptors.
Proadrenomedullin N-terminal 20 peptide: minimal active region to regulate nicotinic receptors.
复制标题
肾上腺髓质素原 N 端 20 肽：调节烟碱受体的最小活性区域。
DOI：
10.1161/01.hyp.32.5.907
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发表时间：
1998
期刊：
影响因子：
--
通讯作者：
O'Connor,DT
中科院分区：
文献类型：
--
作者：
Mahata,M;Mahata,SK;Parmer,RJ;O'Connor,DT
—Proadrenomedullin N-terminal 20 peptide (PAMP-[1-20]; ARLDVASEFRKKWNKWALSR-amide) is a potent hypotensive and catecholamine release–inhibitory peptide released from chromaffin cells. We studied the mechanism of PAMP action and how its function is linked to structure. We tested human PAMP-[1-20] on catecholamine secretion in PC12 pheochromocytoma cells and found it to be a potent, dose-dependent (IC50≈350 nmol/L) secretory inhibitor. Inhibition was specific for nicotinic cholinergic stimulation since PAMP-[1-20] failed to inhibit release by agents that bypass the nicotinic receptor. Nicotinic cationic (22Na+,45Ca2+) signal transduction was disrupted by this peptide, and potencies for inhibition of22Na+uptake and catecholamine secretion were comparable. Even high-dose nicotine failed to overcome the inhibition, suggesting noncompetitive nicotinic antagonism. N- and C-terminal PAMP truncation peptides indicated a role for the C-terminal amide and refined the minimal active region to the C-terminal 8 amino acids (WNKWALSR-amide), a region likely to be α-helical. PAMP also blocked (EC50≈270 nmol/L) nicotinic cholinergic agonist desensitization of catecholamine release, as well as desensitization of nicotinic signal transduction (22Na+uptake). Thus, PAMP may exert both inhibitory and facilitatory effects on nicotinic signaling, depending on the prior state of nicotinic stimulation. PAMP may therefore contribute to a novel, autocrine, homeostatic (negative-feedback) mechanism controlling catecholamine release.
