Background Pharmacological studies using selective P2Y1 antagonists, such as MRS2500, and studies with P2Y1−/− knockout mice have demonstrated that purinergic neuromuscular transmission is mediated by P2Y1 receptors in the colon. The aim of the present study was to test whether P2Y1 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 P2Y1−/− 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 P2Y1−/− mice, a nitrergic IJP (Nω-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 P2Y1−/− mice 2- nitrergic neurotransmission was preserved in both groups. Moreover, 1- spontaneous IJP (MRS2500-sensitive) could be recorded in WT, but not in P2Y1−/− mice 2- MRS2365 a P2Y1 agonist caused smooth muscle hyperpolarization in WT, but not in P2Y1−/− animals, and 3- β-NAD caused smooth muscle hyperpolarization both in WT and P2Y1−/− animals.
Conclusions & Inferences 1- P2Y1 receptor is the general mechanism of purinergic inhibition in the gastrointestinal tract, 2- P2Y1−/− mouse is a useful animal model to study selective impairment of purinergic neurotransmission and 3- P2Y1−/− mouse might help in the identification of purinergic neurotransmitter(s).