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Published on: September 18, 2014
Mechanical responses evoked by nerve stimulation in gastric muscles of mouse lacking inositol trisphosphate receptor
H Takano1, K Imaeda, Y Yamamoto
1Department of Physiology, Nagoya City University Medical School, Japan.
Abstract:
Alteration of mechanical responses elicited by transmural nerve stimulation (TNS) was investigated in pylorus muscle of stomach isolated from mutant mice lacking expression of IP, type-1 receptor. In wild and mutant mice. TNS inhibited spontaneous contractions and generated an off-response at the cessation. The effects of inhibitors of neurotransmission revealed that in wild mice, acetylcholine and nitric oxide were involved as excitatory and inhibitory mediators, respectively. In mutant mice, a lack of nitroxidergic component with associated attenuation of cholinergic transmission was found. The off-response was inhibited by apamin in both mice. In mutant mice, spantide-sensitive excitatory response appeared in the presence of apamin. Acetylcholine and substance P enhanced while noradrenaline and sodium nitroprusside inhibited spontaneous contractions, in both wild and mutant mice; the actions were weaker in mutant mice than in wild mice for any agonists. The results indicate that pylorus smooth muscles receive cholinergic excitatory and nitroxidergic and non-adrenergic non-cholinergic inhibitory projections, and a lack of IP, type-1 receptor results in an impairment of cholinergic and nitroxidergic components, with no alteration of non-adrenergic non-cholinergic inhibitory projections. In addition, the mutation induces a substance P projection which is not detected in wild mice.
Insights
Mice lacking the IP, type-1 receptor show impaired stomach pylorus nerve responses. This impacts acetylcholine and nitric oxide signaling, altering muscle contractions.
Area of Science:
- Gastroenterology
- Neurogastroenterology
- Pharmacology
Background:
- The stomach pylorus plays a crucial role in regulating gastric emptying.
- Nerve stimulation influences pyloric smooth muscle function through various neurotransmitters.
- The IP, type-1 receptor's role in pyloric neurotransmission is not well understood.
Purpose of the Study:
- To investigate the role of the IP, type-1 receptor in regulating pyloric smooth muscle mechanical responses to nerve stimulation.
- To elucidate the specific neurotransmitter pathways involved in pyloric function in wild-type and mutant mice lacking the IP, type-1 receptor.
Main Methods:
- Transmural nerve stimulation (TNS) was applied to isolated pylorus muscle from wild-type and mutant mice.
- Pharmacological agents, including neurotransmission inhibitors (e.g., apamin, spantide), were used to identify mediator roles.
- Changes in spontaneous contractions and off-responses were measured to assess mechanical activity.
Main Results:
- TNS inhibited spontaneous contractions and caused an off-response in both wild-type and mutant mice.
- In wild-type mice, acetylcholine (excitatory) and nitric oxide (inhibitory) were identified as key mediators.
- Mutant mice exhibited attenuated cholinergic transmission and a lack of the nitroxidergic component, with substance P appearing as a novel excitatory mediator.
Conclusions:
- Pyloric smooth muscle receives cholinergic excitatory and nitroxidergic/non-adrenergic non-cholinergic inhibitory inputs.
- Absence of the IP, type-1 receptor impairs cholinergic and nitroxidergic pathways but not non-adrenergic non-cholinergic inhibition.
- Mutation induces a substance P-mediated excitatory projection in the pylorus, not present in wild-type mice.
