The pharmacological characterization of P2X receptors in rat pulmonary artery

Life Sciences 2007 (2007) Proc Life Sciences, PC364

Poster Communications: The pharmacological characterization of P2X receptors in rat pulmonary artery

N. H. Syed1, C. Kennedy1

1. University of Strathclyde, Glasgow, United Kingdom.

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P2X receptors are ligand-gated cation channels that are activated by adenosine 5-triphosphate (ATP) and expressed throughout the body (North, 2002). The P2X agonist α,β-methyleneATP (α,β-meATP) evokes vasoconstriction of the rat isolated large (LPA) and small (SPA) pulmonary arteries, but possibly via different P2X receptor subtypes (Chootip et al., 2002). The aim of this study was to further characterise and compare the pharmacological properties of the P2X receptors present in rat LPA and SPA. 5 mm rings of rat LPA and SPA were mounted under isometric conditions in 1ml baths at 37°C and at resting tensions of 1g and 0.5g respectively. In some tissues the endothelium was removed by gentle rubbing of the intima. Tension was recorded by Grass FT 03 transducers connected to a Powerlab/4e system (AD Instruments). Contractions were elicited by addition of α,β-meATP to the bath. Data are expressed as mean ± sem and were compared by Student’s t-test, one-way ANOVA and Tukey’s comparison or two-way ANOVA as appropriate. Concentration-inhibition response curves for antagonists were fitted to the data by logistic (Hill equation), non-linear regression analysis. α,β-meATP (10 μM) evoked reproducible contractions of LPA and SPA rings and the peak amplitudes were unaffected by removal of the endothelium. However, the combined mean responses in the LPA (250± 27 mg, n=13) were significantly greater than those of the SPA (144± 11 mg, n=13) (P<0.0001). The contractions were not maintained in the continued presence of α,β-meATP and initially decayed at a similar rate in both tissues. However, on repeated administration of α,β-meATP, the decay of the contraction in the SPA became significantly faster than the LPA (decay from peak at 5 min: SPA- 53.7±8.1%, LPA- 19.8±5.5%, P<0.05). In both preparations α,β-meATP (100 μM) induced significantly greater contractions than 10 μM α,β-meATP (n=6, P PPADS=suramin (LPA- n=3-5, SPA- n=3-7). There was no significant difference in the potency of any antagonist in the LPA compared to the SPA. Thus, these data show that α,β-meATP evokes reproducible, transient contractile responses, with a similar pharmacological profile in the rat SPA and LPA. Furthermore, this profile is consistent with the expression of the P2X1 receptor subtype along the length of the rat pulmonary arteries.



Where applicable, experiments conform with Society ethical requirements.

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