Multiple P2Y receptors couple to calcium-dependent, chloride channels in smooth muscle cells of the rat pulmonary artery

Krongkarn Chootip, Alison M. Gurney, Charles Kennedy

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Abstract

Uridine 5'-triphosphate (UTP) and uridine 5'-diphosphate (UDP) act via P2Y receptors to evoke contraction of rat pulmonary arteries, whilst adenosine 5'-triphosphate (ATP) acts via P2X and P2Y receptors. Pharmacological characterisation of these receptors in intact arteries is complicated by release and extracellular metabolism of nucleotides, so the aim of this study was to characterise the P2Y receptors under conditions that minimise these problems. ATP, UTP and UDP (10-4M) evoked oscillating, inward currents (peak = 13-727 pA) in 71-93% of cells. The first current was usually the largest and in the SPA the response to ATP was significantly greater than those to UTP or UDP (P < 0.05). Subsequent currents tended to decrease in amplitude, with a variable time-course, to a level that was significantly smaller for ATP (P < 0.05), UTP (P < 0.001) and UDP (P < 0.05) in the SPA. The frequency of oscillations was similar for each agonist (mean≈6-11.min-1) and changed little during agonist application. The non-selective P2 receptor antagonist suramin (10-4M) abolished currents evoked by ATP in SPA (n = 4) and LPA (n = 4), but pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (PPADS) (10-4M), also a non-selective P2 antagonist, had no effect (n = 4, 5 respectively). Currents elicited by UTP (n = 37) or UDP (n = 14) were unaffected by either antagonist. Contractions of SPA evoked by ATP were partially inhibited by PPADS (n = 4) and abolished by suramin (n = 5). Both antagonists abolished the contractions in LPA.
Original languageEnglish
Article number124
JournalRespiratory Research
Volume6
DOIs
Publication statusPublished - 26 Oct 2005

Keywords

  • pulmonary artery
  • physiology
  • P2Y receptors
  • calcium dependent
  • chloride channels
  • smooth muscle cells
  • rat pulmonary artery
  • multiple p2y receptors

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