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Am J Physiol Cell Physiol 287: C1747-C1752, 2004. First published August 25, 2004; doi:10.1152/ajpcell.00236.2004
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RECEPTORS AND SIGNAL TRANSDUCTION

Contribution of coupling between human myometrial {beta}2-adrenoreceptor and the BKCa channel to uterine quiescence

Boonsri Chanrachakul, Fiona Broughton Pipkin, and Raheela N. Khan

Center for Reproduction and Early Life, Institute of Clinical Research, University of Nottingham, Nottingham NG7 2RD, United Kingdom

Submitted 12 May 2004 ; accepted in final form 17 August 2004

The {beta}2-adrenergic receptor ({beta}2-AR) and the large-conductance Ca2+-activated K+ (BKCa) channel have been shown, separately, to be involved in mediating uterine relaxation. Our recent studies reveal that the levels of both {beta}2-AR and BKCa channel proteins in pregnant human myometrium decrease by ~50% after the onset of labor. We present direct evidence in support of a structural and functional association between the {beta}2-AR and the BKCa channel in pregnant human myometrium. Localization of both proteins is predominantly plasmalemmal, with 60% of {beta}2-AR colocalizing with the BKCa channel. Coimmunoprecipitation studies indicate that BKCa and {beta}2-AR are structurally linked by direct protein-protein interactions. Functional correlation was confirmed by experiments of human myometrial contractility in which the BKCa channel blocker, paxilline, significantly antagonized the relaxant effect of the {beta}2-AR agonist ritodrine. These novel findings provide an insight into the coupling between the {beta}2-AR and BKCa channel and may have utility in the application of this signaling cascade for therapeutic potential in the management of preterm labor.

{beta}2-adrenergic receptor; myometrium; potassium channel; preterm labor; uterine contraction



Address for reprint requests and other correspondence: R. N. Khan, Center for Reproduction and Early Life, Institute of Clinical Research, Univ. Of Nottingham, Academic Division of Obstetrics and Gynaecology, The Medical School, Derby City General Hospital, Uttoxeter New Road, Derby DE22 3DT, UK (E-mail: raheela.khan{at}nottingham.ac.uk)




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