title: Evidence that the ATP-induced increase in vasomotion of guinea-pig mesenteric lymphatics involves an endothelium-dependent release of thromboxane A2.
abstract: 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 (3x10-5 M) but not PPADS (3x10-5 M) abolished the excitatory response to 10-6 M ATP confirming an involvement of P2 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 (3x10-6 M) or SQ29548 (3x10-7 M), inhibitors of specific G proteins, phospholipase A2, cyclo-oxygenase and thromboxane A2 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 NG-nitro-L-arginine (L-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 P2 purinoceptors which because of an involvement of a pertussis toxin sensitive G-protein may be of the P2Y receptor subtype. Their stimulation increases synthesis of phospholipase A2 and production of thromboxane A2, an arachidonic acid metabolite which acts as an endothelium-derived excitatory factor.
authors.affiliation: The Neuroscience Group, Discipline of Human Physiology, Faculty of Medicine & Health Sciences, The University of Newcastle, Callaghan, NSW, 2308, Australia.
authors.forename: J
authors.initials: J
authors.lastname: Gao
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.forename: S E
authors.initials: SE
authors.lastname: Rayner
authors.forename: D F
authors.initials: DF
authors.lastname: Van Helden
mesh_terms: D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D004729:Endothelium, Lymphatic / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008221:Lymphoid Tissue / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008643:Mesentery / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052250:Nitric Oxide Synthase Type III; D019335:Nitroarginine / Q000494:pharmacology; D018048:Receptors, Purinergic P2 / Q000187:drug effects; D013618:Tachyphylaxis; D013928:Thromboxane A2 / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D018048:Receptors, Purinergic P2; D019335:Nitroarginine; D009569:Nitric Oxide; D013928:Thromboxane A2; D000255:Adenosine Triphosphate; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III