ATP-induced endothelium-independent enhancement of lymphatic vasomotion in guinea-pig mesentery involves P2X and P2Y receptors.
1. The present study has investigated mechanisms underlying ATP-induced endothelium-independent enhancement of vasomotion in guinea-pig mesenteric lymphatic vessels. 2. Lymphatic vasomotion, vessel tone and smooth muscle [Ca(2+)](i) showed similar ATP concentration-response curves. 3. ATP, at 0.1 mM, caused a biphasic increase in tonic [Ca(2+)](i) and superimposed vasomotion-associated Ca(2+) transients. All ATP-induced [Ca(2+)](i) changes were abolished by incubating the smooth muscle with suramin (0.1 mM). 4. alpha,beta-MeATP (0.1 mM) and UTP (0.1 mM) caused similar changes in [Ca(2+)](i) but the responses to these agonists were smaller than to ATP. 5. The actions of alpha,beta-MeATP (0.1 mM) were inhibited by suramin (0.1 mM) and PPADS (30 micro M) but not by reactive blue 2 (30 micro M). 6. In the presence of alpha,beta-MeATP (0.1 mM), the increases in tonic [Ca(2+)](i) and vasomotion-associated Ca(2+) transients induced by ATP (0.1 mM) were inhibited by U73122 (5 micro M), CPA (20 micro M) and heparin, whereas U73343 (5 micro M) and pre-treatment with PTx (100 ng ml(-1)) had no significant effects. 7. Depletion of the intracellular stores with CPA (20 micro M) caused an increase in [Ca(2+)](i), which was not blocked by desensitization of P(2X) receptors with alpha,beta-MeATP. 8. The data indicate that ATP, at relatively high concentrations increases lymphatic smooth muscle [Ca(2+)](i) and vasomotion through activation of P(2X1) and P(2Y2) purinoceptors present on lymphatic smooth muscle. The increase in [Ca(2+)](i) is likely to result from Ca(2+) release from inositol-1,4,5-trisphosphate-sensitive stores as well as Ca(2+) influx through store-operated channels and P(2X)-gated channels.
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects / Q000502:physiology; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008208:Lymphatic System / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008643:Mesentery / Q000187:drug effects / Q000502:physiology; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D058469:Receptors, Purinergic P2X; D058473:Receptors, Purinergic P2Y2; D014666:Vasomotor System / Q000187:drug effects* / Q000502:physiology
D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D058473:Receptors, Purinergic P2Y2; D000255:Adenosine Triphosphate