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 [Ca²⁺]i showed similar ATP concentration-response curves. 3. ATP, at 0.1 mM, caused a biphasic increase in tonic [Ca²⁺]i and superimposed vasomotion-associated Ca²⁺ transients. All ATP-induced [Ca²⁺]i changes were abolished by incubating the smooth muscle with suramin (0.1 mM). 4. α,β-MeATP (0.1 mM) and UTP (0.1 mM) caused similar changes in [Ca²⁺]i but the responses to these agonists were smaller than to ATP. 5. The actions of α,β-MeATP (0.1 mM) were inhibited by suramin (0.1 mM) and PPADS (30 μM) but not by reactive blue 2 (30 μM). 6. In the presence of α,β-MeATP (0.1 mM), the increases in tonic [Ca²⁺]i and vasomotion-associated Ca²⁺ transients induced by ATP (0.1 mM) were inhibited by U73122 (5 μM), CPA (20 μM) and heparin, whereas U73343 (5 μM) and pre-treatment with PTx (100 ng ml⁻¹) had no significant effects. 7. Depletion of the intracellular stores with CPA (20 μM) caused an increase in [Ca²⁺]i, which was not blocked by desensitization of P₂x receptors with α,β-MeATP. 8. The data indicate that ATP, at relatively high concentrations increases lymphatic smooth muscle [Ca²⁺]i and vasomotion through activation of P₂x₁ and P₂y₂ purinoceptors present on lymphatic smooth muscle. The increase in [Ca²⁺]i is likely to result from Ca²⁺ release from inositol-1,4,5-trisphosphate-sensitive stores as well as Ca²⁺ influx through store-operated channels and P₂x-gated channels.
British Journal of Pharmacology Vol. 137, Issue 4, p. 477-487