ATP‐induced endothelium‐independent enhancement of lymphatic vasomotion in guinea‐pig mesentery involves P2X and P2Y receptors

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Abstract
The present study has investigated mechanisms underlying ATP‐induced endothelium‐independent enhancement of vasomotion in guinea‐pig mesenteric lymphatic vessels. Lymphatic vasomotion, vessel tone and smooth muscle [Ca2+]i showed similar ATP concentration‐response curves. 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). 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. 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). 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. 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. 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 (2002) 137, 477–487. doi:10.1038/sj.bjp.0704899

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