Purinergic neuromuscular transmission is absent in the colon of P2Y <inf>1</inf> knocked out mice

Diana Gallego, Víctor Gil, Míriam Martínez-Cutillas, Noemí Mañé, Maria Teresa Martín, Marcel Jiménez

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72 Citations (Scopus)


Purinergic and nitrergic co-transmission is the dominant mechanism responsible for neural-mediated smooth muscle relaxation in the gastrointestinal tract. The aim of the present paper was to test whether or not P2Y 1 receptors are involved in purinergic neurotransmission using P2Y 1-/- knock-out mice. Tension and microelectrode recordings were performed on colonic strips. In wild type (WT) animals, electrical field stimulation (EFS) caused an inhibitory junction potential (IJP) that consisted of a fast IJP (MRS2500 sensitive, 1 μm) followed by a sustained IJP (N ω-nitro-l-arginine (l-NNA) sensitive, 1 mm). The fast component of the IJP was absent in P2Y 1-/- mice whereas the sustained IJP (l-NNA sensitive) was recorded. In WT animals, EFS-induced inhibition of spontaneous motility was blocked by the consecutive addition of l-NNA and MRS2500. In P2Y 1-/- mice, EFS responses were completely blocked by l-NNA. In WT and P2Y 1-/- animals, l-NNA induced a smooth muscle depolarization but 'spontaneous' IJP (MRS2500 sensitive) could be recorded in WT but not in P2Y 1-/- animals. Finally, in WT animals, 1 μm MRS2365 caused a smooth muscle hyperpolarization that was blocked by 1 μm MRS2500. In contrast, 1 μm MRS2365 did not modify smooth muscle resting membrane potential in P2Y 1-/- mice. β-Nicotinamide adenine dinucleotide (β-NAD, 1 mm) partially mimicked the effect of MRS2365. We conclude that P2Y 1 receptors mediate purinergic neurotransmission in the gastrointestinal tract and β-NAD partially fulfils the criteria to participate in rodent purinergic neurotransmission. The P2Y 1-/- mouse is a useful animal model to study the selective loss of purinergic neurotransmission. © 2012 The Authors. The Journal of Physiology © 2012 The Physiological Society.
Original languageEnglish
Pages (from-to)1943-1956
JournalJournal of Physiology
Publication statusPublished - 1 Apr 2012


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