Histamine modulates contraction and cyclic nucleotides in cultured rat mesangial cells. Differential effects mediated by histamine H1 and H2 receptors.
Histamine modulates contraction and cyclic nucleotides in cultured rat mesangial cells. Differential effects mediated by histamine H1 and H2 receptors.
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组胺调节培养的大鼠系膜细胞的收缩和环核苷酸。
DOI：
10.1172/jci111876
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
H. Abboud
中科院分区：
文献类型：
--
作者：
J. Sedor;H. Abboud
组胺影响肾小球微循环并调节免疫炎症反应。在大鼠肾脏中，组胺由肾小球合成并刺激肾小球中特异性的环核苷酸产生。我们研究了组胺对体外培养的大鼠肾小球系膜细胞和上皮细胞中环核苷酸积累的影响。组胺刺激培养的肾小球系膜细胞中cAMP的积累（64.0 +/- 22.1至511.4 +/- 86.6 pmol/mg蛋白，n = 9），但对上皮细胞中cAMP的积累没有影响。这种作用具有剂量依赖性和时间依赖性。在5 × 10（-6）M-10（-4）M组胺浓度范围内，cAMP蓄积受到刺激，半数最大刺激效应为2 × 10（-5）M。H2受体拮抗剂西咪替丁（10（-4）M）可消除组胺（10（-4）M）的刺激作用，而等摩尔浓度的H1受体拮抗剂苯海拉明对cAMP积累无明显影响。此外，特定的H2激动剂二甲双胍，但不是H1激动剂2-吡啶基乙胺，刺激cAMP的积累。组胺对上皮细胞中cAMP的积聚或上皮细胞或系膜细胞中环磷酸鸟苷的积聚没有影响。由于在体内输注组胺降低超滤系数，并且由于系膜细胞收缩被认为是造成超滤系数降低的原因，因此我们研究了组胺对系膜细胞收缩特性的影响。组胺（5 × 10（-6）-10（-4）M）使系膜细胞收缩，H1拮抗剂苯海拉明（10（-4）M）而不是H2拮抗剂西咪替丁（10（-4）M）阻止组胺（10（-4）M）诱导的收缩。此外，H1激动剂2-吡啶基乙胺，但不是H2激动剂二甲双胍，收缩系膜细胞。组胺及其特异性激动剂和拮抗剂诱导的收缩孤立的肾小球平面表面积的方式平行于他们对系膜细胞的影响进行评估。Ca ~（++）通道阻断剂桂利嗪（10（-5）M）或无Ca ~（++）、Mg ~（++）的培养液可抑制组胺（10（-4）M）诱导的系膜细胞和肾小球收缩。因此，组胺通过H2受体特异性地增强系膜细胞中的cAMP积累。相比之下，组胺通过H1受体收缩系膜细胞和肾小球，这种作用依赖于细胞外Ca++进入。这些发现表明，组胺可能通过影响系膜细胞收缩来影响肾小球内血流动力学。此外，我们的研究结果认为，在体内观察，组胺降低kf通过和H1受体提供进一步的支持的假设，系膜细胞收缩调节肾小球毛细血管表面积可用于过滤。我们的研究还表明，组胺的这种收缩作用依赖于细胞外钙。对组胺敏感的cAMP系统的存在可能在炎症性肾小球病的发病机制中具有重要意义。肾小球系膜细胞具有与循环和组织免疫效应细胞相似的特征，包括溶酶体酶释放、氧自由基产生和许多免疫调节因子的释放。组胺和cAMP已显示出调节炎性细胞的这些特征。因此，可以想象，组胺，通过其与H2受体和随后产生的cAMP的相互作用，可能对肾小球系膜细胞的这些性质具有深远的影响，这表明这种autacoid不仅可以调节肾小球血流动力学，而且还可以调节免疫，肾小球内的炎症反应。
Histamine influences the glomerular microcirculation and modulates immune-inflammatory responses. In the rat kidney, histamine is synthesized by glomeruli and stimulates cyclic nucleotide production specifically in glomeruli. We investigated the in vitro effect of histamine on cyclic nucleotide accumulation in rat cultured glomerular mesangial and epithelial cells. Histamine stimulated cyclic AMP (cAMP) accumulation in cultured mesangial cells (64.0 +/- 22.1 to 511.4 +/- 86.6 pmol/mg protein, n = 9) but had no effect on cAMP accumulation in epithelial cells. This effect was dose-dependent and time-dependent. Stimulation of cAMP accumulation occurred in the range of 5 X 10(-6) M-10(-4) M histamine with a half maximal stimulatory effect of 2 X 10(-5) M. Initial stimulation was noted by 30 s, and maximum stimulation was observed at 5 min. The H2 antagonist cimetidine (10(-4) M) abolished the stimulatory effect of histamine (10(-4) M), while equimolar concentrations of the H1 antagonist diphenhydramine had no significant effect on cAMP accumulation. Moreover, the specific H2 agonist dimaprit, but not the H1 agonist 2-pyridylethylamine, stimulated cAMP accumulation. Histamine had no effect on cAMP accumulation in epithelial cells or on cyclic guanosine monophosphate accumulation in epithelial or mesangial cells. Since the in vivo infusion of histamine reduces ultrafiltration coefficient and since mesangial cell contraction is thought to be responsible for the reduction in the ultrafiltration coefficient, we examined the effect of histamine on the contractile property of mesangial cells. Histamine (5 X 10(-6)-10(-4) M) contracted mesangial cells, and the H1 antagonist diphenhydramine (10(-4) M) but not the H2 antagonist cimetidine (10(-4) M) prevented histamine (10(-4) M) induced contraction. In addition, the H1 agonist 2-pyridylethylamine, but not the H2 agonist dimaprit, contracted mesangial cells. Histamine and its specific agonists and antagonists induced contraction of isolated glomeruli as assessed by glomerular planar surface area in a manner parallel to their effect on mesangial cells. Cinnarizine (10(-5) M), a Ca++ channel blocker, or Ca++, Mg++-free medium prevented histamine (10(-4) M) induced mesangial cell and glomerular contraction. Thus, histamine enhances cAMP accumulation specifically in mesangial cells via an H2 receptor. In contrast, histamine contracts mesangial cells and glomeruli via an H1 receptor, an effect that is dependent on extracellular Ca++ entry. These findings show that histamine potentially influences intraglomerular hemodynamics via effects on mesangial cell contraction. Moreover, our findings considered with the in vivo observation that histamine reduces kf via and H1 receptor provide further support of the hypothesis that mesangial cell contraction regulates the glomerular capillary surface area available for filtration. Our studies also show that this contractile effect of histamine is dependent on extracellular calcium. The presence of a cAMP system sensitive to histamine may have major implications in the pathogenesis of inflammatory glomerulopathies. Mesangial cells possess characteristics similar to circulating and tissue immune effector cells, including lysosomal enzyme release, oxygen radical production, and release of a number of immunomodulatory factors. Histamine and cAMP have been shown to modulate such characteristics of inflammatory cells. It is therefore conceivable that histamine, via its interaction with H2 receptors and subsequent generation cAMP, may have profound effects on such properties of mesangial cells, suggesting that this autacoid may modulate not only glomerular hemodynamics but also immune, inflammatory responses within the glomerulus.
DOI：
10.1172/jci110931
发表时间：
1983-06
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
L. Scharschmidt;M. Dunn
通讯作者：
L. Scharschmidt;M. Dunn
花生四烯酸代谢和肾小球功能的控制。
DOI：
--
发表时间：
1983
期刊：
Federation proceedings
影响因子：
--
作者：
Scharschmidt,LA;Lianos,E;Dunn,MJ
通讯作者：
Dunn,MJ
离体大鼠肾小球中前列腺素和肾素-血管紧张素系统的相互作用。
DOI：
10.1152/ajprenal.1980.239.6.f602
发表时间：
1980
期刊：
The American journal of physiology
影响因子：
--
作者：
Beierwaltes,WH;Schryver,S;Olson,PS;Romero,JC
通讯作者：
Romero,JC