Proadrenomedullin N‐Terminal 20 Peptide (PAMP), an Endogenous Anticholinergic Peptide: Its Exocytotic Secretion and Inhibition of Catecholamine Secretion in Adrenal Medulla
Proadrenomedullin N‐Terminal 20 Peptide (PAMP), an Endogenous Anticholinergic Peptide: Its Exocytotic Secretion and Inhibition of Catecholamine Secretion in Adrenal Medulla
复制标题
肾上腺髓质素原 N 端 20 肽 (PAMP)，一种内源性抗胆碱能肽：其胞吐分泌和对肾上腺髓质儿茶酚胺分泌的抑制
作者：
F. Katoh;K. Kitamura;H. Niina;R. Yamamoto;H. Washimine;K. Kangawa;Yoshitaka Yamamoto;Hideyuki Kobayashi;T. Eto;A. Wada
摘要：在培养的牛肾上腺髓质细胞中，卡巴胆碱对烟碱受体的刺激诱发了肾上腺髓质素前体N末端20肽（PAMP）（EC 50 = 50.1 µM）和儿茶酚胺（EC 50 = 63.0 µM）的Ca 2+依赖性胞吐共分泌，分泌的PAMP/儿茶酚胺的摩尔比等于细胞中的比例。添加PAMP[1-20] NH 2以非竞争性方式抑制卡巴胆碱通过烟碱受体诱导的22 Na+内流（IC 50 = 2.5 µM），从而减少卡巴胆碱通过电压依赖性Ca 2+通道诱导的45 Ca 2+内流（IC 50 = 1.0 µM）和儿茶酚胺分泌（IC 50 = 1.6 µM）。它不改变高K+通过电压依赖性Ca 2+通道诱导的45 Ca 2+内流或藜芦碱通过电压依赖性Na+通道诱导的22 Na+内流。PAMP似乎是一种新型的抗烟碱肽，通过响应烟碱受体刺激的Ca 2+依赖性胞吐作用与儿茶酚胺共同分泌。
Abstract: In cultured bovine adrenal medullary cells, stimulation of nicotinic receptors by carbachol evoked the Ca2+‐dependent exocytotic cosecretion of proadrenomedullin N‐terminal 20 peptide (PAMP) (EC50 = 50.1 µM) and catecholamines (EC50 = 63.0 µM), with the molar ratio of PAMP/catecholamines secreted being equal to the ratio in the cells. Addition of PAMP[1–20]NH2 inhibited carbachol‐induced 22Na+ influx via nicotinic receptors (IC50 = 2.5 µM) in a noncompetitive manner and thereby reduced carbachol‐induced 45Ca2+ influx via voltage‐dependent Ca2+ channels (IC50 = 1.0 µM) and catecholamine secretion (IC50 = 1.6 µM). It did not alter high K+‐induced 45Ca2+ influx via voltage‐dependent Ca2+ channels or veratridine‐induced 22Na+ influx via voltage‐dependent Na+ channels. PAMP seems to be a novel antinicotinic peptide cosecreted with catecholamines by a Ca2+‐dependent exocytosis in response to nicotinic receptor stimulation.