Ca2+-signalling pathways involved in P2X receptor-induced contractions of rat small pulmonary artery

N.H. Syed, C. Kennedy

Research output: Contribution to journalConference Contribution

Abstract

P2X receptors are Ca2+-permeable, ligand-gated cation channels, which are activated by ATP. In arteries, including the rat small pulmonary artery (SPA), they elicit vasoconstriction (Chootip et al., 2002), which is dependent upon extracellular Ca2+. The aim of this study was to determine the relative contributions of Ca2+influx via the P2X receptor pore and voltage-dependent CaV1.2 (L-type) Ca2+channels, and the role of Ca2+-induced Ca2+release (CICR) in P2X receptor-mediated contractions of rat SPA. 5 mm rings of rat SPA were mounted under isometric conditions in 1ml organ baths at 37°C and a resting tension of 0.5 g. Contractions were elicited by addition of the P2X receptor agonist a,b-meATP (10 lM) or KCl (40 mM) to the bath. Data are expressed as mean ± SEM and were compared by Student's t-test or one-way ANOVA as appropriate. Contractions evoked by a,bmeATP were abolished when tissues were bathed in Ca2+-free buffer (n = 5) and inhibited by 56 ± 6% by nifedipine (1 lM) (n = 5, P < 0.05), 47 ± 9% by CdCl2, (100 lM) (n = 5, P < 0.05) and 56 ± 9% by nifedipine (1 lM) plus CdCl2, (100 lM) (n = 6, P < 0.01). These treatments each abolished contractions evoked by KCl (n = 4-5). To study the role of CICR, the sarcoplasmic Ca2+stores were depleted by pretreatment with ryanodine (10 lM) and caffeine (10 mM). Under these conditions the contractions to a,b-meATP were unchanged (99.9 ± 7.5% of control, n = 7), whereas the response to KCl was significantly reduced (54.4 ± 3.6% of control, n = 5, P < 0.05). These data show that P2X-evoked contraction of SPA predominantly depends equally upon influx of extracellular Ca2+through the P2X receptor pore and CaV1.2 voltage-operated Ca2+channels. However, CICR from sarcoplasmic reticulum Ca2+stores does not appear to play a role.
Original languageEnglish
Pages (from-to)76-76
Number of pages0
JournalFundamental and Clinical Pharmacology
Volume22
Issue numberS2
DOIs
Publication statusPublished - Aug 2008

Keywords

  • Ca2+-signalling pathways
  • P2X
  • receptor-induced contractions
  • rat
  • small pulmonary artery
  • ligand-gated cation channels
  • ATP

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