Human Reproduction, Vol. 11, No. 10, pp. 2285-2290, 1996
© 1996 European Society of Human Reproduction and Embryology
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Pregnancy: Activation of protein kinase C is required for oxytocin-induced contractility in human pregnant myometrium
1Department of Obstetrics and Gynaecology, University College London Medical School Chemes Mews, London, WC1E 6HX 2Reproductive Physiopathology Group, Centre for Clinical Research in Immunology and Signalling and Department of Obstetrics and Gynaecology, University of Birmingham, The Medical School Edgbaston, Birmingham B15 2TT 3Department of Obstetrics and Gynaecology, University of Cambridge, Rosie Maternity Hospital Robinson Way, Cambridge CB2 2SW, UK
Correspondence: 4To whom correspondence should be addressed at: Department of Obstetrics and Gynaecology, Birmingham Maternity Hospital, Edgbaston, Birmingham, B15 2TG, UK
Intracellular mediators regulating the initiation of parturition are not fully understood. This study was designed to determine the possible mechanism of oxytocin-induced uterine contractility during labour. In-vitro isometric contraction studies were performed with longitudinal strips of human pregnant myometrium in the presence and absence of the protein kinase C inhibitors, staurosporine and RO 31–8220, and the tyrosine kinase inhibitor, genistein. Phospholipase D activity was measured by employing the transphosphatidylation reaction. Staurosporine significantly reduced oxytocin-stimulated contractile activity with mean activity reduced by >50% following the addition of 10–6M staurosporine (P < 0.01), while addition of 10–5 M resulted in a measured mean contractile activity of –10% of the control (P < 0.001, n = 5). Similarly, uterine activity was minimal with oxytocin application following incubation with RO 31–8220, mean contractile activity being reduced by -40% by the addition of 10–7 M RO 31–8220 (P < 0.05) and by –87% by the addition of either 10–6 or 10–5 M (P < 0.01, n = 3). Conversely, addition of genistein (10–7 and 10–6 M) had little effect on oxytocin-induced contractions, although at a higher concentration (10–5 M) a significant reduction in oxytocin-induced contractile activity was observed (P < 0.01). Oxytocin evoked phospholipase D activation in a concentration- and time-dependent manner in cultured human pregnant myometrial cells (n = 4). These results indicate that activation of protein kinase C and tyrosine kinase are involved in the regulation of oxytocin-mediated myometrial contractile activity and that a coupled phospholipase D/phosphatidate phosphohydrolase pathway may play a role in the sustained stimulation of myometrial activity during labour.
Key words: myometrium/oxytocin/parturition/phospholipase D/protein kinase C
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