Three distinct muscarinic signalling pathways for cationic channel activation in mouse gut smooth muscle cells

Sakamoto, Takashi; Unno, Toshihiro; Kitazawa, Takio; Taneike, Tetsuro; Yamada, Masahisa; Wess, Jürgen; Nishimura, Masakazu; Komori, Seiichi

doi:10.1113/jphysiol.2007.133165

Cited by 38 publications

(74 citation statements)

References 53 publications

(106 reference statements)

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“…A unique feature of the mI CAT is that it requires simultaneous activation of both the M2 and M3 muscarinic receptors. Conversely, cationic channel activation in murine gut smooth muscle cells involves three separate pathways (24 (40). Whether activation of these channels is by direct interaction with G␣ i/o subunits as shown here for TRPC4/TRPC5 remains to be determined.…”

Section: Discussionmentioning

confidence: 99%

“…In these cells, PTX-sensitive G-proteins but not G␤␥ were suggested to mediate channel activation (22,23). At the level of M2 or M3 muscarinic receptors, Sakamoto et al (24) showed three distinct signaling pathways that activate cationic channels in murine gut smooth muscle cells. The three pathways include the M2, M3, and M2/M3 pathways and were demonstrated using M2 KO, M3 KO, and M2/M3 double KO mice, respectively.…”

Section: Transient Receptor Potential Canonical (Trpc)mentioning

confidence: 99%

“…The three pathways include the M2, M3, and M2/M3 pathways and were demonstrated using M2 KO, M3 KO, and M2/M3 double KO mice, respectively. In addition, the M2/M3 pathway but not the M2 or M3 pathways involves processes in which Ca 2ϩ has a potentiating effect on channel activation, suggesting that the M3 pathway may facilitate the function of the M2/M3 pathway through inositol 1,4,5-trisphosphate-induced Ca 2ϩ release (24). Similarly, activation of mI CAT requires the simultaneous activation of both the M2 and M3 muscarinic receptors (20), further suggesting involvement of G␣ i in channel activation.…”

Section: Transient Receptor Potential Canonical (Trpc)mentioning

confidence: 99%

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Selective Gαi Subunits as Novel Direct Activators of Transient Receptor Potential Canonical (TRPC)4 and TRPC5 Channels

Jeon

Hong

Park

et al. 2012

Journal of Biological Chemistry

103

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Section: Discussionmentioning

confidence: 99%

Section: Transient Receptor Potential Canonical (Trpc)mentioning

confidence: 99%

Section: Transient Receptor Potential Canonical (Trpc)mentioning

confidence: 99%

See 1 more Smart Citation

Selective Gαi Subunits as Novel Direct Activators of Transient Receptor Potential Canonical (TRPC)4 and TRPC5 Channels

Jeon

Hong

Park

et al. 2012

Journal of Biological Chemistry

103

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“…This is also true for the opening of muscarinic receptoroperated cation channels causing depolarization [19] and for the suppression of voltage-gated Ca 2+ channel activity which may serve to prevent Ca 2+ -overloading during muscarinic stimulation [25]. However, intracellular Ca 2+ release [19] or Ca 2+ sensitization (this study) is mediated solely by …”

Section: Discussionmentioning

confidence: 78%

“…Rho, via acting on Rho kinase, causes phosphorylation of MLCP to inhibit its activity and thereby induces Ca 2+ sensitization of contractile proteins. Various muscarinic responses of intestinal smooth muscles have been characterized by using muscarinic receptor subtype-KO mice [19,30,31]. Although mRNA for all five muscarinic receptor subtypes (M 1 -M 5 ) has been found in gut smooth muscles [20], only M 2 and M 3 receptors have been shown to mediate muscarinic responses in gut smooth muscles so far.…”

Section: Discussionmentioning

confidence: 99%

Muscarinic Receptor Subtypes Mediating Ca2+ Sensitization of Intestinal Smooth Muscle Contraction: Studies with Receptor Knockout Mice

Suguro

Matsuyama

Tanahashi

et al. 2010

The Journal of Veterinary Medical Science

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ABSTRACT. In the present study, we have characterized muscarinic receptor subtypes that mediate carbachol-induced Ca 2+ sensitization of contraction in intestinal smooth muscle, using mutant mice lacking M 2 or M 3 muscarinic receptors or both receptor subtypes. In -toxinpermeabilized muscle strips from wild-type (WT) mice, isometric tension responses to Ca 2+ applied cumulatively (pCa 7.0-5.0) were increased when the muscarinic agonist carbachol (100 M) was added to the medium, as judged from shifts of pCa-tension curves in both 50% effective concentration (EC 50 ) and maximum response (E max ) of pCa-tension curve. In preparations from M 2 -knockout (KO) mice, pCa-tension curves were also shifted by carbachol (100 M), and the extents of the EC 50 and E max changes resembled those observed in preparations from WT mice. In preparations from M 3 -KO or M 2 /M 3 -double KO mice, however, no significant changes in pCa-tension curves were obtained after carbachol application. ] c to increase the MLCK/ MLCP activity ratio, resulting in enhanced contractions compared to those without receptor activation [21].In intestinal smooth muscles, acetylcholine and its derivatives such as carbachol, activate muscarinic receptors, inducing Ca 2+ sensitization as well as cytosolic Ca 2+ mobilization and contraction [6,29]. Among the five muscarinic receptor subtypes (M 1 -M 5 ), the M 2 and M 3 are predominantly expressed in intestinal smooth muscles [2]. By using muscarinic receptor antagonists with limited subtype selectivity, Murthy et al. [14] suggested that acetylcholineinduced Rho kinase activation and PKC activation in rabbit intestinal smooth muscles is mediated by the M 3 subtype, leading to Ca 2+ sensitization. However, such pharmacological studies often remain inconclusive because of the poor subtype selectivity of available muscarinic antagonists. For example, pharmacological studies suggested that carbacholevoked contractions are exclusively mediated by M 3 receptors, whereas recent studies using muscarinic receptor knockout mice implicated both M 3 and M 2 receptors in this response [30,31].Therefore, in the present study, using M 2 -knockout (KO) or M 3 -KO or M 2 /M 3 -double KO mice and wild type (WT) mice, we examined the activity of carbachol in inducing Ca 2+ sensitization in -toxin-permeabilized smooth muscles of the small intestine. In general, M 2 and M 3 muscarinic receptors are coupled preferentially with G i/o -and G q/11 -type G-proteins, respectively. We also examined whether the carbacholinduced Ca 2+ sensitization was affected by YM-254890, a selective inhibitor of G q/11 -type G-protein activity [23,26].

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Muscarinic Regulation of Gastrointestinal Motility

Tanahashi,

Kitazawa,

Unno

2024

Neuromethods

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Three distinct muscarinic signalling pathways for cationic channel activation in mouse gut smooth muscle cells

Cited by 38 publications

References 53 publications

Selective Gαi Subunits as Novel Direct Activators of Transient Receptor Potential Canonical (TRPC)4 and TRPC5 Channels

Selective Gαi Subunits as Novel Direct Activators of Transient Receptor Potential Canonical (TRPC)4 and TRPC5 Channels

Muscarinic Receptor Subtypes Mediating Ca2+ Sensitization of Intestinal Smooth Muscle Contraction: Studies with Receptor Knockout Mice

Muscarinic Regulation of Gastrointestinal Motility

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