Macrophages express functional receptors for calcitonin-gene-related peptide.
Macrophages express functional receptors for calcitonin-gene-related peptide.
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巨噬细胞表达降钙素基因相关肽的功能性受体。
DOI：
10.1002/jcp.1041490217
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发表时间：
1991
影响因子：
5.6
通讯作者：
Ganz,MB
中科院分区：
文献类型：
--
作者：
Vignery,A;Wang,F;Ganz,MB
本研究旨在探讨非活化巨噬细胞是否表达降钙素(CT)或降钙素基因相关肽(CGRP)受体。为此，我们首先分析了CT和CGRP是否诱导巨噬细胞内cAMP积聚。巨噬细胞在存在或不存在IBMX的情况下，以增加CT或CGRP的浓度处理2min。CAMP对CGRP的作用呈剂量依赖性，1 nM的CGRP对cAMP的作用达到一半最大。CT在所有剂量下均不能诱导cAMP积聚。用pH敏感染料2，7-双羧乙基-5(6)-羧基荧光素(BCECF)用荧光分光光度法研究了CT和CGRP对Na-H交换器活性的影响。巨噬细胞在无HCO3溶液(HEPES缓冲)中的稳态pH为7.04±0.08(n=22)。在NH4+/NH3酸负荷后，pH的恢复被Na+的去除或添加阿米洛利类似物EIPA所抑制；因此，恢复依赖于Na-H交换活性。CT对稳态pH无影响，但CGRP呈剂量依赖性地升高pH i(10−12~10−6M)。降钙素基因相关肽引起的pH变化是由于降钙素基因相关肽将酸负荷的恢复率(dpHi/dt)从45.3dpHi/dt提高到77.2msEip1(n=8，P<；0.002)，并被μ完全阻断，从而引起Na-H交换器的刺激。这些数据表明，CGRP既增强了Na-H交换器的活性，又增加了细胞内cAMP，从而证明巨噬细胞表达功能性的CGRP受体。
The present study was designed to investigate whether non‐activated macrophages express calcitonin (CT) or calcitonin‐gene‐related peptide (CGRP) receptors. To this end, we first analyzed whether CT and CGRP induce a cAMP accumulation in macrophages. Macrophages were treated for 2 min with increasing concentrations of either CT or CGRP in the presence or absence of IBMX. A dose‐dependent cAMP accumulation was measured in response to CGRP with a half‐maximal effect attained with 1 nM CGRP. CT failed at all doses to induce an accumulation of cAMP. The effects of CT and CGRP on the activation of the Na‐H exchanger were next assessed by spectrofluorometry by using the pH‐sensitive dye 2,7 biscarboxyethyl‐5(6)‐carboxyfluorescein (BCECF). Steadystate pHiof macrophages in a 7.4, HCO3‐free solution (HEPES‐buffered) was 7.04 ± 0.08 (n = 22). pHirecovery following an NH4+/NH3acid load was inhibited by the removal of Na+or by the addition of the amiloride analog EIPA; therefore recovery is dependent on Na‐H exchange activity. CT had no effect on steady‐state pHibut CGRP increased pHiin a dose‐dependent fashion (10−12to 10−6M). The pHichange induced by CGRP was due to the stimulation of the Na‐H exchanger as CGRP enhanced the rate of recovery (dpHi/dt) from an acid load from 45.3 to 77.2 μMs−1(n = 8, P < 0.002) and was completely blocked by EIPA. These data indicate that CGRP both enhances the activity of the Na‐H exchanger and increases intracellular cAMP, thus demonstrating that macrophages express functional CGRP receptors.