ATP‐induced endothelium‐independent enhancement of lymphatic vasomotion in guinea‐pig mesentery involves P 2X and P 2Y receptors

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 [Ca 2+ ] i showed similar ATP concentration‐response curves. ATP, at 0.1 m M , 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 m M ). α,β‐MeATP (0.1 m M ) and UTP (0.1 m M ) caused similar changes in [Ca 2+ ] i but the responses to these agonists were smaller than to ATP. The actions of α,β‐MeATP (0.1 m M ) were inhibited by suramin (0.1 m M ) and PPADS (30 μ M ) but not by reactive blue 2 (30 μ M ). In the presence of α,β‐MeATP (0.1 m M ), the increases in tonic [Ca 2+ ] i and vasomotion‐associated Ca 2+ transients induced by ATP (0.1 m M ) were inhibited by U73122 (5 μ M ), CPA (20 μ M ) and heparin, whereas U73343 (5 μ M ) and pre‐treatment with PTx (100 ng ml −1 ) had no significant effects. Depletion of the intracellular stores with CPA (20 μ M ) caused an increase in [Ca 2+ ] i , which was not blocked by desensitization of P 2X receptors with α,β‐MeATP. 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.British Journal of Pharmacology (2002) 137 , 477–487. doi: 10.1038/sj.bjp.0704899