Abstract
Studying the mechanism(s) of uterine relaxation is important and will be helpful in the prevention of obstetric difficulties such as preterm labour, which remains a major cause of perinatal mortality and morbidity. Multiple signalling pathways regulate the balance between maintaining relative uterine quiescence during gestation, and the transition to the contractile state at the onset of parturition. Elevation of intracellular cyclic AMP promotes myometrial relaxation, and thus quiescence, via effects on multiple intracellular targets including calcium channels, potassium channels and myosin light chain kinase. A complete understanding of cAMP regulatory pathways (synthesis and hydrolysis) would assist in the development of better tocolytics to delay or inhibit preterm labour. Here we review the enzymes involved in cAMP homoeostasis (adenylyl cyclases and phosphodiesterases) and possible myometrial substrates for the cAMP dependent protein kinase. We must emphasise the need to identify novel pharmacological targets in human pregnant myometrium to achieve safe and selective uterine relaxation when this is indicated in preterm labour or other obstetric complications.
Highlights
Preterm labour is a major reproductive health problem due to a high incidence of severe short- and long-term infant morbidity
The use of tocolytic drugs, including those that operate through cyclic AMP such as beta-mimetics, to inhibit uterine contractility in preterm labour is controversial because there is no evidence that currently available drugs improve long term neonatal outcome
The role of cyclic adenosine monophosphate (cAMP) as an important mediator in the regulation of myometrial function is beyond dispute
Summary
Preterm labour is a major reproductive health problem due to a high incidence of severe short- and long-term infant morbidity. The use of tocolytic drugs, including those that operate through cyclic AMP such as beta-mimetics, to inhibit uterine contractility in preterm labour is controversial because there is no evidence that currently available drugs improve long term neonatal outcome. BMC Pregnancy and Childbirth 2007, 7(Suppl 1):S10 http://www.biomedcentral.com/1471-2393/7/S1/S10 It is not known whether the cause of preterm labour is the premature loss of uterine quiescence (e.g. removal of inhibitory factors), or the induction of uterine contractility (e.g. release of stimulatory mediators) or a combination of both [2]. Spatial and temporal changes in cAMP levels can be translated into compartmentalised responses by PRKA anchoring proteins which bind other protein kinases and PDE isoforms to regulate a variety of signalling activities including feedback phosphorylation of ADCY [7]. Physiological roles (see Shabb (2001) [38]) Protein substrate (HUGO nomenclature)
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