Dopaminergic D1-like receptor-dependent inhibition of tyrosine hydroxylase mRNA expression and catecholamine production in human lymphocytes
Dopaminergic D1-like receptor-dependent inhibition of tyrosine hydroxylase mRNA expression and catecholamine production in human lymphocytes
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DOI：
10.1016/j.bcp.2003.10.004
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发表时间：
2004-03-01
影响因子：
5.8
通讯作者：
Frigo, G
中科院分区：
文献类型：
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作者：
Ferrari, M;Cosentino, M;Frigo, G
人外周血单核细胞（PBMC）的活化通过酪氨酸羟化酶（TH; EC 1.14.16.2）的蛋白激酶（PK）C依赖性诱导触发儿茶酚胺（CA）的内源性产生，酪氨酸羟化酶是CA合成中的第一个限速酶。由于CA本身是免疫系统的神经输入的主要介质，我们已经研究了它们的能力，影响PKC诱导的TH mRNA的表达和CA生产在人分离的PBMC。在T-和B-淋巴细胞（但不是单核细胞）中，PKC激活剂12-O-十四烷酰基佛波醇-13-乙酸酯（TPA）（但不是其无活性类似物4 α-佛波醇-12，13-二癸酸酯）诱导TH mRNA表达，随后细胞内CA量增加。人PBMC与多巴胺（DA）（但不与去甲肾上腺素或肾上腺素）共孵育可抑制TPA诱导的TH mRNA表达。DA的作用是浓度依赖性的，并且被多巴胺能D-1样受体激动剂SKF-38393模拟，但不被D-2样受体激动剂溴隐亭模拟。D（1）受体拮抗剂SCH-23390使DA和SKF-38393的浓度-反应曲线右移，而D-2受体拮抗剂多潘立酮、α（1）受体拮抗剂哌唑嗪、α（2）受体拮抗剂育亨宾、或β-肾上腺素能受体拮抗剂普萘洛尔影响DA的抑制作用的任何显着程度。SKF-38393也显着降低TPA-诱导细胞内CA增加，SCH-23390可拮抗该作用。因此，在人T-和β-淋巴细胞中，PKC激活导致TH mRNA表达和随后的细胞内CA增加，这可以被D-1样受体激活抑制。抑制人PBMC中的细胞内CA产生通过减少活化诱导的细胞凋亡来促进细胞存活。因此，TH表达和细胞内CA含量的多巴胺能调节可能代表神经和免疫系统之间以及免疫系统细胞之间的串扰的新机制。(C)2003年爱思唯尔公司All rights reserved.
Activation of human peripheral blood mononuclear cells (PBMC) triggers endogenous production of catecholamines (CA) through protein kinase (PK) C-dependent induction of tyrosine hydroxylase (TH; EC 1.14.16.2), the first and rate-limiting enzyme in the synthesis of CA. Since CA themselves are major mediators of the neural input to the immune system, we have examined their ability to affect PKC-induced TH mRNA expression and CA production in human isolated PBMC. In T- and B-lymphocytes (but not in monocytes) the PKC activator 12-O-tetradecanoylphorbol-13-acetate (TPA) (but not its inactive analogue 4alpha-phorbol-12,13-didecanoate) induced TH mRNA expression which was followed by an increase in the amount of intracellular CA. Coincubation of human PBMC with dopamine (DA) (but not with norepinephrine or epinephrine) inhibited TPA-induced TH mRNA expression. The effect of DA was concentration-dependent and was mimicked by the dopaminergic D-1-like receptor agonist SKF-38393 but not by the D-2-like receptor agonist bromocriptine. The D(1-)like antagonist SCH-23390 shifted to the right the concentration-response curves of both DA and SKF-38393, while neither the D-2-like antagonist domperidone, nor the alpha(1)-adrenoceptor antagonist prazosin, the alpha(2)-adrenoceptor antagonist yohimbine, or the beta-adrenoceptor antagonist propranolol affected to any significant extent the inhibitory effect of DA. SKF-38393 also significantly reduced TPA-induced increase of intracellular CA, an effect which was antagonized by SCH-23390. It is thus suggested that in human T- and beta-lymphocytes PKC activation leads to TH mRNA expression and subsequent increase of intracellular CA, which can be inhibited by D-1-like receptor activation. Inhibition of intracellular CA production in human PBMC promotes cell survival through reduction of activation-induced apoptosis. and dopaminergic modulation of TH expression and intracellular CA content may thus represent a novel mechanism in the cross-talk between the nervous and the immune system as well as among immune system cells. (C) 2003 Elsevier Inc. All rights reserved.