Roles of M<sub>2</sub> and M<sub>3</sub> muscarinic receptors in the generation of rhythmic motor activity in mouse small intestine

Tanahashi, Yasuyuki; Waki, N.; Unno, Toshihiro; Matsuyama, Hayato; Iino, Satoshi; Kitazawa, Takio; Yamada, Masahisa; Komori, Seiichi

doi:10.1111/nmo.12194

Cited by 15 publications

(14 citation statements)

References 50 publications

(96 reference statements)

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“…Correspondingly, parasympathetic terminals release acetylcholine to muscarinic receptors and finally contract the smooth muscle. Although five muscarinic receptor subtypes (M 1–5 ) have been recognized in the gastrointestinal tract, the M 2 and M 3 muscarinic receptor subtypes are found with preponderance [31]. Thus, we performed beta-adrenoceptors antagonist and agonist to investigate the role of sympathetic pathway as well as muscarinic receptors antagonist and agonist for parasympathetic pathway in rats.…”

Section: Discussionmentioning

confidence: 99%

Electroacupuncture at ST37 Enhances Jejunal Motility via Excitation of the Parasympathetic System in Rats and Mice

Yuan

Wang

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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Background. The roles of the sympathetic and parasympathetic systems in mediating the effect of electroacupuncture (EA) at ST37 on jejunal motility have yet to be demonstrated. Aim. We used rats and mice to investigate the effect and mechanism of action of EA at ST37 on jejunal motility. Methods. Jejunal motility was recorded by a balloon placed in the jejunum and connected to a biological signal collection system through a transducer. The effects of EA (3 mA) at ST37 were evaluated in Sprague-Dawley rats without drugs and with the administration of clenbuterol, propranolol, acetylcholine, and atropine. Further, the efficacy of EA at different intensities (1/2/4/6/8 mA) was measured in wild-type mice and β 1 β 2 −/− mice and M2M3 −/− mice. Results. In Sprague-Dawley rats, the excitatory effect of EA at ST37 on jejunal motility disappeared in the presence of the muscarinic receptor antagonist atropine. EA at ST37 was less effective in M2M3 −/− mice than in wild-type mice. Furthermore, to a certain extent, there existed “intensity-response” relationship between jejunal motility and EA. Conclusions. EA at ST37 can enhance jejunal motility in rats and mice mainly via excitation of the parasympathetic pathway. There is an “intensity-response” relationship between EA and effect on jejunal motility.

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Section: Discussionmentioning

confidence: 99%

Electroacupuncture at ST37 Enhances Jejunal Motility via Excitation of the Parasympathetic System in Rats and Mice

Yuan

Wang

et al. 2016

Evidence-Based Complementary and Alternative Medicine

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“…Tanahashi et al (2013) [111] found complex differences in the peristaltic movements among isolated small intestine from mAChR-KO and wild-type mice. Changes in intraluminal pressure (IP; representing circular muscle activity) and longitudinal muscle tension (LT) produced by luminal distension were simultaneously measured in the gut segments.…”

Section: In Vivo and In Vitro Gastrointestinal Motilitymentioning

confidence: 99%

Functions of Muscarinic Receptor Subtypes in Gastrointestinal Smooth Muscle: A Review of Studies with Receptor-Knockout Mice

Tanahashi

Komori

Matsuyama

et al. 2021

IJMS

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Parasympathetic signalling via muscarinic acetylcholine receptors (mAChRs) regulates gastrointestinal smooth muscle function. In most instances, the mAChR population in smooth muscle consists mainly of M2 and M3 subtypes in a roughly 80% to 20% mixture. Stimulation of these mAChRs triggers a complex array of biochemical and electrical events in the cell via associated G proteins, leading to smooth muscle contraction and facilitating gastrointestinal motility. Major signalling events induced by mAChRs include adenylyl cyclase inhibition, phosphoinositide hydrolysis, intracellular Ca2+ mobilisation, myofilament Ca2+ sensitisation, generation of non-selective cationic and chloride currents, K+ current modulation, inhibition or potentiation of voltage-dependent Ca2+ currents and membrane depolarisation. A lack of ligands with a high degree of receptor subtype selectivity and the frequent contribution of multiple receptor subtypes to responses in the same cell type have hampered studies on the signal transduction mechanisms and functions of individual mAChR subtypes. Therefore, novel strategies such as genetic manipulation are required to elucidate both the contributions of specific AChR subtypes to smooth muscle function and the underlying molecular mechanisms. In this article, we review recent studies on muscarinic function in gastrointestinal smooth muscle using mAChR subtype-knockout mice.

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“…Basal release of nitric oxide needs to be accompanied by other neuronal factor(s), likely associated with excitatory innervation. Cholinergic excitation is likely involved in the generation of the minute rhythm motor pattern in the mouse small intestine under most conditions (Tanahashi et al, 2013). Distentioninduced rhythmic motor activity at 1.4/min in wild type mice was blocked in most preparations by atropine and in most but not all M 2 KO or M 3 KO mice, indicating an important but not essential role of cholinergic activation; occurrence of another excitatory FIGURE 9 | Effect of carbenoxolone on clusters and gaps in the presence of SNP.…”

Section: Simultaneous Excitation Of Cholinergic or Neurokinin Or Seromentioning

confidence: 99%

“…The same p scale shown to the right of panel (B) applies to all graphs. stimulus was also possible, likely a neurokinin (Tanahashi et al, 2013). The cholinergic or neurokinin excitation may be directly affecting smooth muscle cells or be mediated by ICC-DMP.…”

Section: Simultaneous Excitation Of Cholinergic or Neurokinin Or Seromentioning

confidence: 99%

Nitric Oxide Is Essential for Generating the Minute Rhythm Contraction Pattern in the Small Intestine, Likely via ICC-DMP

Parsons

Huizinga

2021

Front. Neurosci.

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Nitrergic nerves have been proposed to play a critical role in the orchestration of peristaltic activities throughout the gastrointestinal tract. In the present study, we investigated the role of nitric oxide, using spatiotemporal mapping, in peristaltic activity of the whole ex vivo mouse intestine. We identified a propulsive motor pattern in the form of propagating myogenic contractions, that are clustered by the enteric nervous system into a minute rhythm that is dependent on nitric oxide. The cluster formation was abolished by TTX, lidocaine and nitric oxide synthesis inhibition, whereas the myogenic contractions, occurring at the ICC-MP initiated slow wave frequency, remained undisturbed. Cluster formation, inhibited by block of nitric oxide synthesis, was fully restored in a highly regular rhythmic fashion by a constant level of nitric oxide generated by sodium nitroprusside; but the action of sodium nitroprusside was inhibited by lidocaine indicating that it was relying on neural activity, but not rhythmic nitrergic nerve activity. Hence, distention-induced activity of cholinergic nerves and/or a co-factor within nitrergic nerves such as ATP is also a requirement for the minute rhythm. Cluster formation was dependent on distention but was not evoked by a distention reflex. Block of gap junction conductance by carbenoxolone, dose dependently inhibited, and eventually abolished clusters and contraction waves, likely associated, not with inhibition of nitrergic innervation, but by abolishing ICC network synchronization. An intriguing feature of the clusters was the presence of bands of rhythmic inhibitions at 4–8 cycles/min; these inhibitory patches occurred in the presence of tetrodotoxin or lidocaine and hence were not dependent on nitrergic nerves. We propose that the minute rhythm is generated by nitric oxide-induced rhythmic depolarization of the musculature via ICC-DMP.

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Roles of M₂ and M₃ muscarinic receptors in the generation of rhythmic motor activity in mouse small intestine

Cited by 15 publications

References 50 publications

Electroacupuncture at ST37 Enhances Jejunal Motility via Excitation of the Parasympathetic System in Rats and Mice

Electroacupuncture at ST37 Enhances Jejunal Motility via Excitation of the Parasympathetic System in Rats and Mice

Functions of Muscarinic Receptor Subtypes in Gastrointestinal Smooth Muscle: A Review of Studies with Receptor-Knockout Mice

Nitric Oxide Is Essential for Generating the Minute Rhythm Contraction Pattern in the Small Intestine, Likely via ICC-DMP

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Roles of M2 and M3 muscarinic receptors in the generation of rhythmic motor activity in mouse small intestine

Cited by 15 publications

References 50 publications

Electroacupuncture at ST37 Enhances Jejunal Motility via Excitation of the Parasympathetic System in Rats and Mice

Electroacupuncture at ST37 Enhances Jejunal Motility via Excitation of the Parasympathetic System in Rats and Mice

Functions of Muscarinic Receptor Subtypes in Gastrointestinal Smooth Muscle: A Review of Studies with Receptor-Knockout Mice

Nitric Oxide Is Essential for Generating the Minute Rhythm Contraction Pattern in the Small Intestine, Likely via ICC-DMP

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Roles of M₂ and M₃ muscarinic receptors in the generation of rhythmic motor activity in mouse small intestine