Evidence map›Paper›PMID 23613531›Full record

ArticleThe Journal of physiology2013

Ca2+ sensitization pathways accessed by cholinergic neurotransmission in the murine gastric fundus.

Bhupal P Bhetwal, Kenton M Sanders, Changlong An, Danielle M Trappanese, Robert S Moreland, Brian A Perrino

Open access · greenAbstract read
In one paragraph

Article in The Journal of physiology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.

0numbers the graph read from it
0cells of the map it votes in
47citing papers in PubMed
4.2field-weighted citation impact, top 5% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

47 citing papers in PubMed, 55 citations in OpenAlex.

  1. Review
  2. Article
  3. CaPhysiological reviews · 2024
    Review
  4. Article
  5. Article
  6. CaAdvances in experimental medicine and biology · 2022
    Article
  7. Article
  8. Article
  9. Mfge8 attenuates human gastric antrum smooth muscle contractions.Journal of muscle research and cell motility · 2021
    Article
  10. Excitatory cholinergic responses in mouse colon intramuscular interstitial cells of Cajal are due to enhanced CaFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2020
    Article
  11. Article
  12. Review
  13. Article
  14. Review
  15. The functional role of protease-activated receptors on contractile responses by activation of CaAmerican journal of physiology. Gastrointestinal and liver physiology · 2018
    Article
  16. Article
  17. Article
  18. Inhibitory Neural Regulation of the CaFrontiers in physiology · 2018
    Article
  19. Article
  20. Article
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 2 institutions in 1 country.

Bhupal P BhetwalUniversity of Nevada School of Medicine, Physiology and Cell Biology, University of Nevada, Reno, CMM203E, Reno, NV 89557, USA.
Kenton M Sanders
Changlong An
Danielle M Trappanese
Robert S Moreland
Brian A Perrino
University of Nevada, Reno · USDrexel University · US

Funding

Tissue, Cell and Tissue Culture CoreP01DK041315 · NIDDK · UNIVERSITY OF NEVADA RENO · PI KEEF, KATHLEEN D · 1989 to 2018
$26.3M
Smooth Muscle Plasticity: A COBREP20GM103513 · NIGMS · UNIVERSITY OF NEVADA RENO · PI SANDERS, KENTON M · 2012 to 2013
$4.1M
Electrical Control of Gastric MotilityR37DK040569 · NIDDK · UNIVERSITY OF NEVADA RENO · PI SANDERS, KENTON M · 2004 to 2013
$3.4M
Excitation contraction coupling in bladder smooth muscleR01DK085734 · NIDDK · DREXEL UNIVERSITY · PI MORELAND, ROBERT S · 2010 to 2013
$1.4M
NIDDK NIH HHS DK41315NIDDK NIH HHS DK85734NIDDK NIH HHS R37 DK040569NIGMS NIH HHS GM103513NIGMS NIH HHS P20 GM103513
6 · The paper itself

Abstract

Ca(2+) sensitization of contraction has typically been investigated by bathing muscles in solutions containing agonists. However, it is unknown whether bath-applied agonists and enteric neurotransmission activate similar Ca(2+) sensitization mechanisms. We investigated protein kinase C (PKC)-potentiated phosphatase inhibitor protein of 17 kDa (CPI-17) and myosin phosphatase targeting subunit 1 (MYPT1) phosphorylation in murine gastric fundus muscles stimulated by bath-applied carbachol (CCh) or cholinergic motor neurotransmission. CCh increased MYPT1 phosphorylation at Thr696 (pT696) and Thr853 (pT853), CPI-17 at Thr38 (pT38), and myosin light chain at Ser19 (pS19). Electrical field stimulation (EFS) only increased pT38. In the presence of neostigmine, EFS increased pT38, pT853 and pS19. In fundus muscles of W/W(v) mice, EFS alone increased pT38 and pT853. Atropine blocked all contractions and all increases in pT696, pT853, pT38 and pS19. The Rho kinase (ROCK) inhibitor SAR1x blocked increases in pT853 and pT696. The PKC inhibitors Go6976 and Gf109203x or nicardipine blocked increases in pT38 and pT696. These findings suggest that cholinergic motor neurotransmission activates PKC-dependent CPI-17 phosphorylation. Bath-applied CCh recruits additional ROCK-dependent MYPT1 phosphorylation due to exposure of the agonist to a wider population of muscarinic receptors. Intramuscular interstitial cells of Cajal (ICC-IMs) and cholinesterases restrict ACh accessibility to a select population of muscarinic receptors, possibly only those expressed by ICC-IMs. These results provide the first biochemical evidence for focalized (or synaptic-like) neurotransmission, rather than diffuse 'volume' neurotransmission in a smooth muscle tissue. Furthermore, these findings demonstrate that bath application of contractile agonists to gastrointestinal smooth muscles does not mimic physiological responses to cholinergic neurotransmission.

Indexed as

Synaptic TransmissionAnimalsCalciumCholinergic FibersElectric StimulationGastric FundusInterstitial Cells of CajalIntracellular Signaling Peptides and ProteinsMaleMiceMice, Inbred C57BLMuscarinic AntagonistsMuscle ContractionMuscle ProteinsMuscle, SmoothMyosin-Light-Chain KinaseCalciumIntracellular Signaling Peptides and ProteinsMuscarinic AntagonistsMuscle ProteinsMyosin-Light-Chain KinaseMyosin-Light-Chain PhosphataseMyosin Light ChainsNeostigminePhosphoproteinsPpp1r12a protein, mousePpp1r14a protein, mouseProtein Kinase Inhibitors

Identifiers

PMID23613531
PMCPMC3832114
OpenAlexW1595159473

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.