ATP-induced endothelium-independent enhancement of lymphatic vasomotion in guinea-pig mesentery involves P_(2X) and P_(2Y) receptors

摘要

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+)]; 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 [Ca~(2+)]_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 (30μM) but not by reactive blue 2 (30μM). 6. In the presence of α, β-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 (5μM), CPA (20μM) and heparin, whereas U73343 (5μM) and pre-treatment with PTx (100 ng ml~(-1)) had no significant effects. 7. Depletion of the intracellular stores with CPA (20μM) caused an increase in [Ca~(2+)]_i, which was not blocked by desensitization of P_(2X) receptors with α, β-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.