Evidence that the ATP-induced increase in vasomotion of guinea-pig mesenteric lymphatics involves an endothelium-dependent release of thromboxane A2

被引:28
作者
Gao, JN [1 ]
Zhao, J [1 ]
Rayner, SE [1 ]
Van Helden, DF [1 ]
机构
[1] Univ Newcastle, Fac Med & Hlth Sci, Discipline Human Physiol, Neurosci Grp, Callaghan, NSW 2308, Australia
关键词
lymphatic vessels; vasomotion; endothelium; ATP; phospholipase A(2); arachidonic acid; thromboxane A(2); P-2Y purinoceptors;
D O I
10.1038/sj.bjp.0702710
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
1 Experiments were made to investigate mechanisms by which adenosine 5'-trisphosphate (ATP) enhanced vasomotion in mesenteric lymphatic vessels isolated from young guinea-pigs. 2 ATP (10(-8)-10(-3) M) caused a concentration-dependent increase of perfusion-induced vasomotion with the endothelium mediating a fundamental role at low ATP concentrations (10(-8)-10(-6) M). 3 The response to 10(-6) M ATP showed tachyphylaxis when applied at intervals of 10 min but not at intervals of 20 or 30 min. 4 Suramin (10(-4) M) or reactive blue 2 (3 x 10(-5) M) but not PPADS (3 x 10(-5) M) abolished the excitatory response to 10(-6) M ATP confirming an involvement of P-2 purinoceptors. 5 The excitatory response to 10(-6) M ATP was abolished by treatment with either pertussis toxin (100 ng ml(-1)), antiflammin-1 (10(-9) M), indomethacin (3 x 10(-6) M) or SQ29548 (3 x 10(-7) M), inhibitors of specific G proteins, phospholipase A(2), cyclo-oxygenase and thromboxane A(2) receptors respectively. 6 ATP simultaneously induced a suramin-sensitive inhibitory response, which was normally masked by the excitatory response. ATP-induced inhibition was mediated by endothelium-derived nitric oxide (EDNO) as the response was abolished by N-G-nitro-L-arginine (r-NOARG; 10(-4) M), an inhibitor of nitric oxide synthase. 7 We conclude that ATP modulates lymphatic vasomotion by endothelium-dependent and endothelium-independent mechanisms. One of these is a dominant excitation caused through endothelial P-2 purinoceptors which because of an involvement of a pertussis toxin sensitive G-protein may be of the P-2Y receptor subtype. Their stimulation increases synthesis of phospholipase A(2) and production of thromboxane A(2), an arachidonic acid metabolite which acts as an endothelium-derived excitatory factor.
引用
收藏
页码:1597 / 1602
页数:6
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