Evidence map›Paper›PMID 21372126›Full record

ArticleThe Journal of biological chemistry2011

Ethanol enhances carbachol-induced protease activation and accelerates Ca2+ waves in isolated rat pancreatic acini.

Abrahim I Orabi, Ahsan U Shah, Kamaldeen Muili, Yuhuan Luo, Syeda Maham Mahmood, Asim Ahmad, Anamika Reed, Sohail Z Husain

Abstract read
In one paragraph

Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.

0numbers the graph read from it
0cells of the map it votes in
16citing papers in PubMed
–field-weighted citation impact
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

16 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Article
  5. The Journal of biological chemistry · 2017
    Article
  6. Animal models of gastrointestinal and liver diseases. Animal models of acute and chronic pancreatitis.American journal of physiology. Gastrointestinal and liver physiology · 2016
    Review
  7. The ryanodine receptor is expressed in human pancreatic acinar cells and contributes to acinar cell injury.American journal of physiology. Gastrointestinal and liver physiology · 2014
    Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Ryanodine receptors contribute to bile acid-induced pathological calcium signaling and pancreatitis in mice.American journal of physiology. Gastrointestinal and liver physiology · 2012
    Article
  15. Article
  16. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Abrahim I OrabiYale University School of Medicine, New Haven, Connecticut 06520, USA.
Ahsan U Shah
Kamaldeen Muili
Yuhuan Luo
Syeda Maham Mahmood
Asim Ahmad
Anamika Reed
Sohail Z Husain

Funding

Yale Liver CenterP30DK034989 · NIDDK · YALE UNIVERSITY · PI WAJAHAT Zafar MEHAL · 1986 to 2026
$31.1M
Developmental Adaptation: Child Health Research CenterK12HD001401 · NICHD · YALE UNIVERSITY · PI BOGUE, CLIFFORD W · 2001 to 2015
$4.2M
Ryanodine Receptor in PancreatitisR01DK083327 · NIDDK · YALE UNIVERSITY · PI HUSAIN, SOHAIL Z · 2009 to 2013
$1.6M
Low ph alters intracellular and extracellular communication in the acinar cellK08DK090104 · NIDDK · YALE UNIVERSITY · PI REED, ANAMIKA MARAGRET · 2011 to 2014
$617k
Calcineurin in Pathologic Zymogen ActivationR03DK078707 · NIDDK · YALE UNIVERSITY · PI HUSAIN, SOHAIL Z · 2008 to 2009
$165k
NICHD NIH HHS K12 HD001401NIDDK NIH HHS DK34989NIDDK NIH HHS K08 DK090104NIDDK NIH HHS P30 DK034989NIDDK NIH HHS R01 DK083327NIDDK NIH HHS R03 DK078707
6 · The paper itself

Abstract

Alcohol abuse is a leading cause of pancreatitis, accounting for 30% of acute cases and 70-90% of chronic cases, yet the mechanisms leading to alcohol-associated pancreatic injury are unclear. An early and critical feature of pancreatitis is the aberrant signaling of Ca(2+) within the pancreatic acinar cell. An important conductor of this Ca(2+) is the basolaterally localized, intracellular Ca(2+) channel ryanodine receptor (RYR). In this study, we examined the effect of ethanol on mediating both pathologic intra-acinar protease activation, a precursor to pancreatitis, as well as RYR Ca(2+) signals. We hypothesized that ethanol sensitizes the acinar cell to protease activation by modulating RYR Ca(2+). Acinar cells were freshly isolated from rat, pretreated with ethanol, and stimulated with the muscarinic agonist carbachol (1 μM). Ethanol caused a doubling in the carbachol-induced activation of the proteases trypsin and chymotrypsin (p < 0.02). The RYR inhibitor dantrolene abrogated the enhancement of trypsin and chymotrypsin activity by ethanol (p < 0.005 for both proteases). Further, ethanol accelerated the speed of the apical to basolateral Ca(2+) wave from 9 to 18 μm/s (p < 0.0005; n = 18-22 cells/group); an increase in Ca(2+) wave speed was also observed with a change from physiologic concentrations of carbachol (1 μM) to a supraphysiologic concentration (1 mM) that leads to protease activation. Dantrolene abrogated the ethanol-induced acceleration of wave speed (p < 0.05; n = 10-16 cells/group). Our results suggest that the enhancement of pathologic protease activation by ethanol is dependent on the RYR and that a novel mechanism for this enhancement may involve RYR-mediated acceleration of Ca(2+) waves.

Indexed as

AlcoholismAnimalsCalciumCarbacholChymotrypsinDantroleneDisease Models, AnimalEthanolMuscle Relaxants, CentralPancreasPeptide HydrolasesRatsRats, Sprague-DawleyRyanodine Receptor Calcium Release ChannelSignal TransductionTrypsinCalciumCarbacholChymotrypsinDantroleneEthanolMuscle Relaxants, CentralPeptide HydrolasesRyanodine Receptor Calcium Release ChannelTrypsin

Identifiers

PMID21372126
PMCPMC3077610

What Socratic 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 Socratic graph.