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Published on: March 5, 2018
P2Y(1) knockout mice lack purinergic neuromuscular transmission in the antrum and cecum
V Gil1, M Martínez-Cutillas, N Mañé
1Department of Cell Biology, Physiology and Immunology and Neuroscience Institute, Universitat Autònoma de Barcelona, Bellaterra, Spain.
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).
Insights
The P2Y(1) receptor mediates purinergic inhibition throughout the gastrointestinal tract. Studies using P2Y(1) knockout mice confirm its role in neurotransmission and provide a model for further research.
Area of Science:
- Gastroenterology
- Neuroscience
- Pharmacology
Background:
- Purinergic neuromuscular transmission in the colon is mediated by P2Y(1) receptors.
- Previous studies utilized P2Y(1) antagonists and knockout mice to establish this role.
Purpose of the Study:
- To investigate the involvement of P2Y(1) receptors in purinergic neurotransmission within the antrum and cecum.
- To determine if P2Y(1) receptor function is conserved across different regions of the gastrointestinal tract.
Main Methods:
- Microelectrode recordings were conducted on antrum and cecum tissue strips from wild-type (WT) and P2Y(1)(-/-) mice.
- Electrical field stimulation was used to elicit inhibitory junction potentials (IJPs).
- Pharmacological agents, including a P2Y(1) antagonist (MRS2500) and agonist (MRS2365), were employed.
Main Results:
- In both antrum and cecum, WT mice exhibited MRS2500-sensitive purinergic inhibitory junction potentials (IJPs), which were absent in P2Y(1)(-/-) mice.
- Nitregic neurotransmission was preserved in P2Y(1)(-/-) mice, indicating selective impairment of purinergic signaling.
- P2Y(1) agonist MRS2365 induced smooth muscle hyperpolarization in WT but not in knockout mice, further confirming P2Y(1) receptor involvement.
Conclusions:
- P2Y(1) receptors are a general mechanism for purinergic inhibition in the gastrointestinal tract.
- P2Y(1)(-/-) mice serve as a valuable model for studying impaired purinergic neurotransmission.
- This animal model facilitates the identification of endogenous purinergic neurotransmitters.
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