ATP participates in the regulation of microvessel permeability
ATP participates in the regulation of microvessel permeability
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DOI：
10.1211/jpp.58.4.0007
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发表时间：
2006-04-01
影响因子：
3.3
通讯作者：
Shinozuka, K
中科院分区：
文献类型：
--
作者：
Tanaka, N;Nejime, N;Shinozuka, K
我们以前证明，P2 Y受体的刺激通过细胞旁途径增强培养的内皮细胞单层的大分子渗透性。为了确定P2 Y受体是否参与完整微血管通透性的调节，我们使用异硫氰酸荧光素-葡聚糖（FD-4; MW 4400; 1.0 mg mL（-1））检测了外源性和内源性ATP对灌流大鼠尾动脉表面组织通透性的影响。通过共聚焦荧光成像系统评估FD-4的渗透。我们发现，2-甲硫基腺苷5 '-三磷酸，一种P2 Y受体激动剂，增强FD-4在大鼠尾动脉组织表面的荧光强度，它被吡哆醛磷酸-6-偶氮苯基-2'，4 '-二磺酸，一种P2受体拮抗剂抑制。此外，去甲肾上腺素，交感神经递质，缓激肽，炎症autacoid，增强FD-4的荧光强度在大鼠尾动脉的表面组织。去甲肾上腺素的增强作用可被P2受体拮抗剂显著抑制。此外，去甲肾上腺素和缓激肽引起大鼠尾动脉内皮细胞释放ATP、ADP、AMP和腺苷。提示外源性和内源性ATP通过P2 Y受体增加毛细血管大分子通透性。这种内皮通透性的嘌呤能调节可能在生理和病理生理条件下起作用。
We demonstrated previously that stimulation of the P2Y receptor enhanced the macromolecular permeability of cultured endothelial cell monolayers via the paracellular pathway. To determine whether the P2Y receptor participates in the regulation of permeability in intact microvessels, we have examined the effects of exogenous and endogenous ATP on the permeation of the surface tissue of perfused rat tail caudal artery using a fluorescein isothiocyanate-dextran (FD-4; MW 4400; 1.0 mg mL(-1)). The permeation of FD-4 was assessed by a confocal fluorescence imaging system. We found that 2-methylthioadenosine 5'-triphosphate, a P2Y receptor agonist, enhanced the fluorescence intensity of FD-4 in the surface of the rat caudal artery tissue and that it was inhibited by pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid, a P2 receptor antagonist. Also, noradrenaline, a sympathetic neurotransmitter, and bradykinin, an inflammatory autacoid, enhanced the fluorescence intensity of FD-4 in the surface tissue of the rat caudal artery. The enhancement by noradrenaline was significantly inhibited by the P2 receptor antagonist. In addition, noradrenaline and bradykinin caused the release of ATP, ADP, AMP and adenosine from the endothelium of the rat caudal artery. These results indicated that the exogenous and endogenous ATP increased the macromolecular permeability of blood capillaries via the P2Y receptor. Such purinergic regulation of endothelial permeability may function in physiological and pathophysiological conditions.