Evidence map›Paper›PMID 18509761›Full record

ArticleJournal of molecular neuroscience : MN2008

Identification of intracellular signaling cascades mediating the PACAP-induced increase in guinea pig cardiac neuron excitability.

John D Tompkins, Rodney L Parsons

Open access · greenAbstract read
In one paragraph

Article in Journal of molecular neuroscience : MN, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
0.7field-weighted citation impact, top 38% 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

13 citing papers in PubMed, 23 citations in OpenAlex.

  1. Article
  2. Article
  3. PACAP signaling in stress: insights from the chromaffin cell.Pflugers Archiv : European journal of physiology · 2018
    Review
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. VIP and PACAP effects on mouse major pelvic ganglia neurons.Journal of molecular neuroscience : MN · 2010
    Article
  11. Article
  12. Remodeling of the guinea pig intrinsic cardiac plexus with chronic pressure overload.American journal of physiology. Regulatory, integrative and comparative physiology · 2009
    Article
  13. 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

2 authors at 1 institution in 1 country.

John D TompkinsDepartment of Anatomy and Neurobiology, College of Medicine, University of Vermont, Burlington, VT 05405, USA. john.tompkins@uvm.edu
Rodney L Parsons
University of Vermont · US

Funding

Center for Neuroscience ExcellenceP30GM103498 · NIGMS · UNIVERSITY OF VERMONT & ST AGRIC COLLEGE · PI PARSONS, RODNEY L · 2012 to 2015
$4.3M
Modulation of parasympathetic neurons by PACAP peptidesR01HL065481 · NHLBI · UNIVERSITY OF VERMONT &ST AGRIC COLLEGE · PI PARSONS, RODNEY L · 2002 to 2005
$1.2M
NHLBI NIH HHS HL65481NHLBI NIH HHS R01 HL065481NIGMS NIH HHS P30 GM103498
6 · The paper itself

Abstract

The pituitary adenylate cyclase-activating polypeptide (PACAP) increases excitability of guinea pig cardiac neurons, an effect mediated through activation of PAC1 receptors. The signaling cascades that couple activation of the PAC1 receptor to alterations in membrane ionic conductances responsible for the PACAP effect are unknown. Intracellular recordings were made from neurons in kinase inhibitor-treated cardiac ganglia preparations to determine which of the intracellular cascades activated by PAC1 receptor stimulation mediate the PACAP effect. In control cells, long depolarizing-current steps elicited one to three action potentials. In contrast, during the application of 10 nM PACAP, depolarizing-current pulses elicited multiple action potential firing (greater than or equal to five action potentials) in 79% of the neurons. Pretreatment with an adenylyl cyclase inhibitor, SQ 22536 (100 microM), suppressed the PACAP-induced increase in excitability, whereas the presence of U-73122 (10 microM), a potent phospholipase C (PLC) inhibitor, had no effect. Thus, the activation of adenylyl cyclase, but not PLC, was a critical step mediating the PACAP effect. Pretreatment with H-89 (1 microM), a protein kinase A inhibitor, and PD 98059 (50 microM), a MEK kinase inhibitor, also significantly blunted the PACAP-induced increase in excitability. Furthermore, treatment with forskolin (5 microM), an activator of adenylyl cyclase, or exposure to the cell-permeable cyclic adenosine monophosphate (cAMP) analogue, 8-bromo-cAMP (1 mM), partially recapitulated the effect of PACAP on excitability. We conclude that the activation of signaling cascades downstream of cAMP mediate the PACAP-induced increase in cardiac neuron excitability.

Indexed as

AdenineAdenylyl Cyclase InhibitorsAdenylyl CyclasesAnimalsCyclic AMP-Dependent Protein KinasesEnzyme InhibitorsEstrenesFlavonoidsGuinea PigsMitogen-Activated Protein KinasesMyocardiumNeuronsParasympathetic Fibers, PostganglionicPituitary Adenylate Cyclase-Activating PolypeptidePyrrolidinonesSignal Transduction1-(6-((3-methoxyestra-1,3,5(10)-trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one9-(tetrahydro-2-furyl)-adenineAdenineAdenylyl Cyclase InhibitorsAdenylyl CyclasesCyclic AMP-Dependent Protein KinasesEnzyme InhibitorsEstrenesFlavonoidsMitogen-Activated Protein KinasesPituitary Adenylate Cyclase-Activating PolypeptidePyrrolidinones

Identifiers

PMID18509761
PMCPMC2748763
OpenAlexW1990361965

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.