P2Y 1 knockout mice lack purinergic neuromuscular transmission in the antrum and cecum

Background  Pharmacological studies using selective P2Y 1 antagonists, such as MRS2500, and studies with P2Y 1 −/− knockout mice have demonstrated that purinergic neuromuscular transmission is mediated by P2Y 1 receptors in the colon. The aim of the present study was to test whether P2Y 1 receptors are involved in purinergic neurotransmission in the antrum and cecum. Methods  Microelectrode recordings were performed on strips from the antrum and cecum of wild type animals (WT) and P2Y 1 −/− mice. Key Results  In the antrum, no differences in resting membrane potential and slow wave activity were observed between groups. In WT animals, electrical field stimulation elicited a MRS2500‐sensitive inhibitory junction potential (IJP). In P2Y 1 −/− mice, a nitrergic IJP ( N ω ‐nitro‐ l ‐arginine‐sensitive), but not a purinergic IJP was recorded. This IJP was equivalent to the response obtained in strips from WT animals previously incubated with MRS2500. Similar results were obtained in the cecum: 1‐ the purinergic IJP (MRS2500‐sensitive) recorded in WT animals was absent in P2Y 1 −/− mice 2‐ nitrergic neurotransmission was preserved in both groups. Moreover, 1‐ spontaneous IJP (MRS2500‐sensitive) could be recorded in WT, but not in P2Y 1 −/− mice 2‐ MRS2365 a P2Y 1 agonist caused smooth muscle hyperpolarization in WT, but not in P2Y 1 −/− animals, and 3‐ β‐NAD caused smooth muscle hyperpolarization both in WT and P2Y 1 −/− animals. Conclusions & Inferences  1‐ P2Y 1 receptor is the general mechanism of purinergic inhibition in the gastrointestinal tract, 2‐ P2Y 1 −/− mouse is a useful animal model to study selective impairment of purinergic neurotransmission and 3‐ P2Y 1 −/− mouse might help in the identification of purinergic neurotransmitter(s).