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March 1, 2006The FASEB Journal

Activation of Epac/Rap1 attenuates venular permeability response to platelet activating factor (PAF) in vivo

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Key result

Pretreatment with O-Me-cAMP significantly attenuated PAF-stimulated hyperpermeability in rat mesentery venules, reducing the peak Lp response from 25-fold to 8-fold over baseline (p<0.05).

Population

single rat mesentery post-capillary venules (n=6)

Comparison

8-pCPT-2'-O-Methyl-cAMP 100 μM or 500 μM, 30 min… vs PAF alone

Design

Preclinical

Authors

RAR. H. AdamsonUniversity of California, DavisJLJudy LyBoston CollegeDDD DrenckhahnPhilipps University of Marburg

Discussion

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Overview

May support Epac pathway targeting in permeability research; leaves open clinical translation from animal data.

Structured PICO

P
Population
6 single rat mesentery post-capillary venules tested for PAF stimulated hyperpermeability.
I
Intervention
8-pCPT-2'-O-Methyl-cAMP (O-Me-cAMP) 100 μM or 500 μM, 30 min pretreatment, followed by platelet activating factor (PAF)
C
Comparator
PAF alone
O
Outcome
hydraulic permeability (Lp)surrogate

Main Result

Absolute Event Rate: 8% vs 25%

p-value: p=<0.05

Activation of the Epac/Rap1 pathway using O-Me-cAMP significantly attenuates PAF-induced hyperpermeability in rat microvessels.

Cite This Study

Adamson et al. (2006) studied PAF stimulated hyperpermeability (n=6). O-Me-cAMP (8-pCPT-2'-O-Methyl-cAMP) vs. PAF alone was evaluated on Hydraulic permeability (Lp) response to PAF (p=<0.05). Pretreatment with O-Me-cAMP significantly attenuated PAF-stimulated hyperpermeability in rat mesentery venules, reducing the peak Lp response from 25-fold to 8-fold over baseline (p<0.05).

synapsesocial.com/papers/6a7074f2f44fa9f079de1bbahttps://doi.org/10.1096/fasebj.20.4.a706-c
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Epac/Rap and PKA are novel mechanisms of ANP‐induced Rac‐mediated pulmonary endothelial barrier protection2007 · 141 citations
  2. 2Exchange protein activated by cAMP (Epac) mediates cAMP‐dependent but protein kinase A‐insensitive modulation of vascular ATP‐sensitive potassium channels2009 · 70 citations
  3. 3Epac1 regulates integrity of endothelial cell junctions through VE‐cadherin2005 · 304 citations
  4. 4Cyclic AMP Phosphodiesterase 4D (PDE4D) Tethers EPAC1 in a Vascular Endothelial Cadherin (VE-Cad)-based Signaling Complex and Controls cAMP-mediated Vascular Permeability2010 · 98 citations
  5. 5cAMP signalling in the vasculature: the role of Epac (exchange protein directly activated by cAMP)2014 · 68 citations