P3.14 Functional roles of M2 and M3 muscarinic receptors in cholinergic nerve-induced contractions in mouse bladder studied with receptor knockout mice

Unno, Toshihiro; Yamamoto, Masayuki; Hayashi, Takao; Koide, Kei; Tanahashi, Yasuyuki; Matsuyama, Hayato; Yamada, Masahisa; Wess, J.; Komori, Seiichi

doi:10.1016/j.autneu.2009.05.162

Cited by 5 publications

(9 citation statements)

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“…The tachykinergic mechanisms may be a back‐up system to compensate the M 2 and M 3 receptor‐mediated mechanisms for the generation of rhythmic activity, in the event muscarinic receptor function is disturbed. This idea is consistent with our previous reports that functional up‐regulation of tachykinergic excitatory neurotransmission occurs in M 2 /M 3 double‐KO mice . The compensatory mechanisms could probably operate in WT preparations, as the rhythmic activity was recovered after its abolition by atropine in the WT preparations (Fig.…”

Section: Discussionsupporting

confidence: 92%

“…We have demonstrated previously that M 2 and M 3 receptors participate in cholinergic nerve‐induced contractions in the mouse ileum, with the M 3 receptors playing a greater role than the M 2 receptors . The outcome of the present study, however, suggested that M 2 receptors are essential for generating the cholinergic rhythmic activity and are responsible for synchronization of the IP and LT rises.…”

Section: Discussioncontrasting

confidence: 63%

“…Many previous studies using various muscarinic receptor antagonists have indicated that M 3 receptors exclusively contribute to the gastrointestinal smooth muscle contractions . However, a recent study with mutant mice lacking the M 2 or M 3 muscarinic receptor subtypes has revealed that both M 3 and M 2 receptors are responsible for the cholinergic nerve‐induced contractions, although the M 3 receptors predominantly contribute to the contractions . In the gut enteric nervous system, M 2 receptors are also expressed in the myenteric ganglia or myenteric nerve fiber, and seem to regulate the release of neurotransmitter(s) .…”

Section: Introductionmentioning

confidence: 99%

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

Tanahashi

Waki²,

Unno

et al. 2013

Neurogastroenterology Motil

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Section: Discussionsupporting

confidence: 92%

Section: Discussioncontrasting

confidence: 63%

Section: Introductionmentioning

confidence: 99%

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

Tanahashi

Waki²,

Unno

et al. 2013

Neurogastroenterology Motil

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“…Treatment of mice with PTX has been shown to prevent CCh from producing M 2 ‐mediated contraction or cation channel currents in gut smooth muscle preparations (Unno et al. , 2005; 2006; Sakamoto et al.…”

Section: Resultsmentioning

confidence: 99%

“…and, 70–74 h later the cells were prepared as described above. This protocol has been used previously for effective blockade of M 2 muscarinic receptor‐mediated contraction of mouse gut smooth muscle (Unno et al. , 2005; 2006).…”

Section: Methodsmentioning

confidence: 99%

Multiple muscarinic pathways mediate the suppression of voltage‐gated Ca²⁺ channels in mouse intestinal smooth muscle cells

Tanahashi

Unno

Matsuyama

et al. 2009

British J Pharmacology

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Background and purpose: Stimulation of muscarinic receptors in intestinal smooth muscle cells results in suppression of voltage-gated Ca 2+ channel currents (ICa). However, little is known about which receptor subtype(s) mediate this effect. Experimental approach: The effect of carbachol on ICa was studied in single intestinal myocytes from M2 or M3 muscarinic receptor knockout (KO) and wild-type (WT) mice. Key results: In M2KO cells, carbachol (100 mM) induced a sustained ICa suppression as seen in WT cells. However, this suppression was significantly smaller than that seen in WT cells. Carbachol also suppressed ICa in M3KO cells, but with a phasic time course. In M2/M3-double KO cells, carbachol had no effect on ICa. The extent of the suppression in WT cells was greater than the sum of the ICa suppressions in M2KO and M3KO cells, indicating that it is not a simple mixture of M2 and M3 receptor responses. The Gi/o inhibitor, Pertussis toxin, abolished the ICa suppression in M3KO cells, but not in M2KO cells. In contrast, the Gq/11 inhibitor YM-254890 strongly inhibited only the ICa suppression in M2KO cells. Suppression of ICa in WT cells was markedly reduced by either Pertussis toxin or YM-254890.

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Atropine-functionalized gold nanoparticles binding to muscarinic receptors after passage across the intestinal epithelium

et al. 2022

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Gold nanoparticles have a high potential to be a treatment of diseases by their specific drug delivery properties and multivalent receptor stimulation. For the present project, spherical gold nanoparticles were synthesized and functionalized with the muscarinic receptor antagonist atropine (Au-MUDA-AT NPs). The diameter of the gold core could precisely be controlled by using different synthetic methods and reducing agents resulting in functionalized gold nanoparticles with diameters ranging from 8 to 16 nm. The ability to interact with intestinal muscarinic receptors is size-dependent. When using intestinal chloride secretion induced by the stable acetylcholine derivative, carbachol, as read-out, the strongest inhibition, i.e. the most efficient blockade of muscarinic receptors, was observed with 13 nm sized Au-MUDA-AT NPs. Functional experiments indicate that Au-MUDA-AT NPs with a diameter of 14 nm are able to pass the intestinal mucosa in a time-dependent manner after administration to the intestinal lumen. For example, luminally administered Au-MUDA-AT NPs inhibited contractions of the small intestinal longitudinal muscle layer induced by electrical stimulation of myenteric neurons. A similar inhibition of basolateral epithelial receptors was observed after luminal administration of Au-MUDA-AT NPs when using carbachol-induced chloride secretion across the intestinal epithelium as a test system. Thus, Au-MUDA-AT NPs might be a therapeutic tool for the modulation of intestinal secretion and motility after oral application in the future.

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P3.14 Functional roles of M2 and M3 muscarinic receptors in cholinergic nerve-induced contractions in mouse bladder studied with receptor knockout mice

Cited by 5 publications

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

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

Multiple muscarinic pathways mediate the suppression of voltage‐gated Ca²⁺ channels in mouse intestinal smooth muscle cells

Atropine-functionalized gold nanoparticles binding to muscarinic receptors after passage across the intestinal epithelium

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P3.14 Functional roles of M2 and M3 muscarinic receptors in cholinergic nerve-induced contractions in mouse bladder studied with receptor knockout mice

Cited by 5 publications

References 0 publications

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

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

Multiple muscarinic pathways mediate the suppression of voltage‐gated Ca2+ channels in mouse intestinal smooth muscle cells

Atropine-functionalized gold nanoparticles binding to muscarinic receptors after passage across the intestinal epithelium

Contact Info

Product

Resources

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

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

Multiple muscarinic pathways mediate the suppression of voltage‐gated Ca²⁺ channels in mouse intestinal smooth muscle cells