Interaction between catecholamines and neuropeptides in the carotid body: evidence for dopamine modulation of neutral endopeptidase activity.
Interaction between catecholamines and neuropeptides in the carotid body: evidence for dopamine modulation of neutral endopeptidase activity.
复制标题
颈动脉体中儿茶酚胺和神经肽之间的相互作用：多巴胺调节中性内肽酶活性的证据。
DOI：
10.1007/0-306-46825-5_49
复制
发表时间：
2000
影响因子：
--
通讯作者：
Lee,MS
中科院分区：
文献类型：
--
作者：
Kumar,GK;Oh,EK;Lee,MS
颈动脉体（CB）含有多种神经化学物质，包括儿茶酚胺（CA）和神经肽。它们参与颈动脉体感觉反应的调节。基于从中枢神经系统的观察，我们假设CA调节CB中的神经肽代谢。为了验证我们的假设，胎牛颈动脉体使用。免疫细胞化学分析表明，胎牛颈动脉体表达酪氨酸羟化酶，和中性内肽酶样免疫反应。为了评估CA的作用，将胎牛颈动脉体的薄片与50 - 500 μM多巴胺（DA）在37°C下孵育1小时。作为神经肽代谢的指标，中性内肽酶（NEP），在CB中的神经肽的主要降解酶的活性测定在颈动脉体的膜富集和可溶性组分。用缺乏DA的培养基孵育的CB作为对照。平均而言，未处理的CB的膜富集部分和可溶性部分的NEP活性分别为4.8 μ mol/h/mg CB和6.7 μ mol/h/mg CB。浓度低于μMxDA时，膜组分的NEP活性增强（−60%），而可溶性组分的NEP活性受到抑制（−62%）。浓度>200 μMxDA时，两种组分的NEP活性均受到抑制。当CB孵育DA在连二亚硫酸钠，氧清除剂，DA的存在下，即使在较高的浓度，刺激NEP活性的膜富集的馏分。上述结果表明，DA调节神经肽代谢CB通过非受体介导的机制，涉及直接与NEP的相互作用。
Carotid body (CB) contains multiple neurochemicals that include catecholamines (CA) and neuropeptides. They are involved in the modulation of sensory response of the carotid body. Based on observations from the central nervous system, we hypothesized that CA modulates neuropeptide metabolism in CB. To test our hypothesis, fetal calf carotid body ued. Immunocytochemical analysis showed that fetal calf carotid body expresses both tyrosine hydroxylase, and neutral endopeptidase-like immunoreactivity. To assess the effect of CA, thin slices of fetal calf carotid body were incubated with 50−500 μM of dopamine (DA) at 37°C for 1 hour. As an index of neuropeptide metabolism, the activity of neutral endopeptidase (NEP), a major degrading enzyme of neuropeptides in CB was determined in the membrane-enriched and soluble fractions of the carotid body. CBs incubated with medium lacking DA served as control. On average, NEP activities of the membrane-enriched, and soluble fractions of the untreated CB were 4.8∓0.2 and 6.7– pmole per hour per mg of CB respectively. At concentrations less than μMxDA enhanced NEP activity of the membrane fraction (−60%) whereas inhibition of NEP was observed in the soluble fraction (−62%) At concentrations >200 μMxDA inhibited NEP activity of the two fractions. When CBs were incubated with DA in the presence of sodium dithionite, an oxygen scavenger, DA, even at higher concentrations, stimulated NEP activity of the membrane-enriched fraction. The above results demonstrate that DA modulates neuropeptide metabolism in CB via a non-receptor-mediated mechanism involving a direct interaction with NEP.