Suvannapura A, Levens N R
Research Department, CIBA-GEIGY Corporation, Summit, New Jersey 07901.
Am J Physiol. 1988 Feb;254(2 Pt 1):G135-41. doi: 10.1152/ajpgi.1988.254.2.G135.
Angiotensin II (ANG II) is believed to stimulate sodium and water absorption from the small intestine by enhancing sympathetic nerve transmission. This study is designed to determine whether ANG II can enhance sympathetic neurotransmission within the small intestine by inhibiting norepinephrine (NE) uptake. Intracellular NE accumulation by rat jejunum was concentration dependent and resolved into high- and low-affinity components. The high-affinity component (uptake 1) exhibited a Michaelis constant (Km) of 1.72 microM and a maximum velocity (Vmax) of 1.19 nmol.g-1.10 min-1. The low-affinity component (uptake 2) exhibited a Km of 111.1 microM and a Vmax of 37.1 nmol.g-1.10 min-1. Cocaine, an inhibitor of neuronal uptake, inhibited the intracellular accumulation of label by 80%. Treatment of animals with 6-hydroxydopamine, which depletes norepinephrine from sympathetic terminals, also attenuated NE uptake by 60%. Thus accumulation within sympathetic nerves constitutes the major form of [3H]NE uptake into rat jejunum. ANG II inhibited intracellular [3H]NE uptake in a concentration-dependent manner. At a dose of 1 mM, ANG II inhibited intracellular [3H]NE accumulation by 60%. Cocaine failed to potentiate the inhibition of [3H]NE uptake produced by ANG II. Thus ANG II appears to prevent [3H]NE accumulation within rat jejunum by inhibiting neuronal uptake.
血管紧张素II(ANG II)被认为可通过增强交感神经传递来刺激小肠对钠和水的吸收。本研究旨在确定ANG II是否能通过抑制去甲肾上腺素(NE)摄取来增强小肠内的交感神经传递。大鼠空肠细胞内NE的积累呈浓度依赖性,并可分为高亲和力和低亲和力成分。高亲和力成分(摄取1)的米氏常数(Km)为1.72微摩尔,最大速度(Vmax)为1.19纳摩尔·克⁻¹·10分钟⁻¹。低亲和力成分(摄取2)的Km为111.1微摩尔,Vmax为37.1纳摩尔·克⁻¹·10分钟⁻¹。神经元摄取抑制剂可卡因可使细胞内标记物的积累减少80%。用6-羟基多巴胺处理动物,可使交感神经末梢的去甲肾上腺素耗竭,也使NE摄取减少60%。因此,交感神经内的积累是大鼠空肠对[³H]NE摄取的主要形式。ANG II以浓度依赖性方式抑制细胞内[³H]NE摄取。在1毫摩尔的剂量下,ANG II可使细胞内[³H]NE积累减少60%。可卡因未能增强ANG II对[³H]NE摄取的抑制作用。因此,ANG II似乎通过抑制神经元摄取来阻止大鼠空肠内[³H]NE的积累。