First Author | Gallego D | Year | 2012 |
Journal | J Physiol | Volume | 590 |
Issue | 8 | Pages | 1943-56 |
PubMed ID | 22371472 | Mgi Jnum | J:195950 |
Mgi Id | MGI:5486265 | Doi | 10.1113/jphysiol.2011.224345 |
Citation | Gallego D, et al. (2012) Purinergic neuromuscular transmission is absent in the colon of P2Y(1) knocked out mice. J Physiol 590(Pt 8):1943-56 |
abstractText | 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 mum) followed by a sustained IJP (N(omega)-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 mum MRS2365 caused a smooth muscle hyperpolarization that was blocked by 1 mum MRS2500. In contrast, 1 mum MRS2365 did not modify smooth muscle resting membrane potential in P2Y(1)(-/-) mice. beta-Nicotinamide adenine dinucleotide (beta-NAD, 1 mm) partially mimicked the effect of MRS2365. We conclude that P2Y(1) receptors mediate purinergic neurotransmission in the gastrointestinal tract and beta-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. |