Imperial College London
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DrPeiLai

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Research Associate
 
 
 
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Contact

 

p.lai

 
 
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Location

 

Chelsea and Westminster HospitalChelsea and Westminster Campus

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Summary

 

Publications

Citation

BibTex format

@article{Lai:2016:10.1113/JP272320,
author = {Lai, PF and Tribe, RM and Johnson, MR},
doi = {10.1113/JP272320},
journal = {Journal of Physiology-London},
pages = {6369--6393},
title = {Differential impact of acute and prolonged cAMP agonist exposure on protein kinase A activation and human myometrium contractile activity},
url = {http://dx.doi.org/10.1113/JP272320},
volume = {594},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Acute cAMP elevation inhibits myometrial contractility, but the mechanisms responsible are not fully defined and the long-term effects uncertain. These need to be defined in pregnant human myometrium before the therapeutic potential of cAMP-elevating agents in the prevention of preterm labour can be realised. In the present study, we tested the hypotheses that PKA activity is necessary for cAMP-induced myometrial relaxation and prolonged cAMP elevation can prevent myometrial contractions. Myometrial tissues obtained from term, pre-labour elective Caesarean sections were exposed to receptor-independent cAMP agonists to determine the relationship between myometrial contractility (spontaneous and oxytocin-induced), PKA activity, HSP20 phosphorylation and expression of contraction-associated and cAMP signalling proteins. Acute (1 h) application of cAMP agonists promoted myometrial relaxation but this was weakly related to PKA activation. PKA-specific activator, 6-Bnz-cAMP, increased PKA activity (6.8 ± 2.0 mean fold versus vehicle; P = 0.0313) without inducing myometrial relaxation. Spontaneous myometrial contractility declined after 24 h but was less marked when tissues were constantly exposed to cAMP agonists, especially for 8-bromo-cAMP (4.3 ± 1.2 mean fold versus vehicle; P = 0.0043); this was associated with changes to calponin, cofilin and HSP20 phosphorylated/total protein levels. Oxytocin-induced contractions were unaffected by pre-incubation with cAMP agonists despite treatments being able to enhance PKA activity and HSP20 phosphorylation. These data suggest that cAMP-induced myometrial relaxation is not solely dependent on PKA activity and the ability of cAMP agonists to repress myometrial contractility is lost with prolonged exposure. We conclude that cAMP agonist treatment alone may not prevent preterm labour.
AU  - Lai,PF
AU  - Tribe,RM
AU  - Johnson,MR
DO  - 10.1113/JP272320
EP  - 6393
PY  - 2016///
SN  - 1469-7793
SP  - 6369
TI  - Differential impact of acute and prolonged cAMP agonist exposure on protein kinase A activation and human myometrium contractile activity
T2  - Journal of Physiology-London
UR  - http://dx.doi.org/10.1113/JP272320
UR  - http://hdl.handle.net/10044/1/39061
VL  - 594
ER  -
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