Inhibitory neurotransmission in the circular muscle layer of mouse colon

Spencer, Nick J.; Bywater, Robert A.R.; Holman, Mollie E.; Taylor, Grahame S.

doi:10.1016/s0165-1838(98)00045-9

Cited by 44 publications

(72 citation statements)

References 10 publications

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“…Therefore, Up4A might participate in tonic purinergic inhibition of colon excitability (25). Unlike the observations in a previous study documenting the release of NAD + (21), stimulation of receptors present in myenteric ganglia caused no detectable release of Up4A.…”

Section: Discussioncontrasting

confidence: 71%

Uridine adenosine tetraphosphate is a novel neurogenic P2Y1 receptor activator in the gut

Durnin

Hwang

Kurahashi

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Section: Discussioncontrasting

confidence: 71%

Uridine adenosine tetraphosphate is a novel neurogenic P2Y1 receptor activator in the gut

Durnin

Hwang

Kurahashi

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…Therefore, we performed additional contractile experiments in the presence of TTX as TTX blocks nerve axonal action potentials. TTX (1 mM) increased the amplitude of spontaneous phasic contractions (tabulated as AUC), confirming that spontaneous activity of enteric inhibitory neurones regulates the basal excitability of murine colonic smooth muscles (Figure 3A and B; Spencer et al, 1998). Application of Y-27632 (10 mM) in the presence of TTX (1 mM) decreased the contractile response to CCh (1 mM) ( Figure 3B-D, N = 4, P < 0.05).…”

Section: Rho-kinase Inhibition Reduced Nerve-stimulated and Cch-inducsupporting

confidence: 68%

Contribution of Rho‐kinase to membrane excitability of murine colonic smooth muscle

Bayguinov

Dwyer

Kim

et al. 2011

British J Pharmacology

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BACKGROUND AND PURPOSEThe Rho-kinase pathway regulates agonist-induced contractions in several smooth muscles, including the intestine, urinary bladder and uterus, via dynamic changes in the Ca 2+ sensitivity of the contractile apparatus. However, there is evidence that Rho-kinase also modulates other cellular effectors such as ion channels. EXPERIMENTAL APPROACHWe examined the regulation of colonic smooth muscle excitability by Rho-kinase using conventional microelectrode recording, isometric force measurements and patch-clamp techniques. KEY RESULTSThe Rho-kinase inhibitors, Y-27632 and H-1152, decreased nerve-evoked on-and off-contractions elicited at a range of frequencies and durations. The Rho-kinase inhibitors decreased the spontaneous contractions and the responses to carbachol and substance P independently of neuronal inputs, suggesting Y-27632 acts directly on smooth muscle. The Rho-kinase inhibitors significantly reduced the depolarization in response to carbachol, an effect that cannot be due to regulation of Ca 2+ sensitization. Patch-clamp experiments showed that Rho-kinase inhibitors reduce GTPgS-activated non-selective cation currents. CONCLUSIONS AND IMPLICATIONSThe Rho-kinase inhibitors decreased contractions evoked by nerve stimulation, carbachol and substance P. These effects were not solely due to inhibition of the Ca 2+ sensitization pathway, as the Rho-kinase inhibitors also inhibited the non-selective cation conductances activated by excitatory transmitters. Thus, Rho-kinase may regulate smooth muscle excitability mechanisms by regulating non-selective cation channels as well as changing the Ca 2+ sensitivity of the contractile apparatus.

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“…The membrane potentials of isolated SMCs and PDGFR␣ ϩ cells were less negative than those recorded from cells in the colonic tunica muscularis in situ (39). However, additional factors affect the input resistances and, therefore, the resting membrane potentials of cells of the SIP syncytium in situ.…”

Section: Discussionmentioning

confidence: 77%

“…Postjunctional effects are mediated by P2Y 1 purinoceptors, blocked completely by specific P2Y 1 receptor antagonists (16,20,33), and absent in muscles of P2ry1 Ϫ/Ϫ mice (15,25). The postjunctional fIJP response depends partially on apaminsensitive ion channels that have been identified as the product(s) of one or more of the paralogs of small-conductance Ca 2ϩ -activated K ϩ (SK) channels (Kcnn1-3) (16,33,39,44).…”

mentioning

confidence: 99%

Platelet-derived growth factor receptor-α-positive cells and not smooth muscle cells mediate purinergic hyperpolarization in murine colonic muscles

Kurahashi

Mutafova‐Yambolieva

Koh

et al. 2014

American Journal of Physiology-Cell Physiology

106

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Enteric inhibitory neurotransmission is an important feature of the neural regulation of gastrointestinal motility. Purinergic neurotransmission, via P2Y1 receptors, mediates one phase of inhibitory neural control. For decades, ATP has been assumed to be the purinergic neurotransmitter and smooth muscle cells (SMCs) have been considered the primary targets for inhibitory neurotransmission. Recent experiments have cast doubt on both of these assumptions and suggested that another cell type, platelet-derived growth factor receptor-α-positive (PDGFRα(+)) cells, is the target for purinergic neurotransmission. We compared responses of PDGFRα(+) cells and SMCs to several purine compounds to determine if these cells responded in a manner consistent with enteric inhibitory neurotransmission. ATP hyperpolarized PDGFRα(+) cells but depolarized SMCs. Only part of the ATP response in PDGFRα(+) cells was blocked by MRS 2500, a P2Y1 antagonist. ADP, MRS 2365, β-NAD, and adenosine 5-diphosphate-ribose, P2Y1 agonists, hyperpolarized PDGFRα(+) cells, and these responses were blocked by MRS 2500. Adenosine 5-diphosphate-ribose was more potent in eliciting hyperpolarization responses than β-NAD. P2Y1 agonists failed to elicit responses in SMCs. Small hyperpolarization responses were elicited in SMCs by a small-conductance Ca(2+)-activated K(+) channel agonist, cyclohexyl-[2-(3,5-dimethyl-pyrazol-1-yl)-6-methyl-pyrimidin-4-yl]-amine, consistent with the low expression and current density of small-conductance Ca(2+)-activated K(+) channels in these cells. Large-amplitude hyperpolarization responses, elicited in PDGFRα(+) cells, but not SMCs, by P2Y1 agonists are consistent with the generation of inhibitory junction potentials in intact muscles in response to purinergic neurotransmission. The responses of PDGFRα(+) cells and SMCs to purines suggest that SMCs are unlikely targets for purinergic neurotransmission in colonic muscles.

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Inhibitory neurotransmission in the circular muscle layer of mouse colon

Cited by 44 publications

References 10 publications

Uridine adenosine tetraphosphate is a novel neurogenic P2Y1 receptor activator in the gut

Uridine adenosine tetraphosphate is a novel neurogenic P2Y1 receptor activator in the gut

Contribution of Rho‐kinase to membrane excitability of murine colonic smooth muscle

Platelet-derived growth factor receptor-α-positive cells and not smooth muscle cells mediate purinergic hyperpolarization in murine colonic muscles

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