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Mechanisms of labour—biochemical aspects
Author(s) -
Bernal Andrés López
Publication year - 2003
Publication title -
bjog: an international journal of obstetrics and gynaecology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.157
H-Index - 164
eISSN - 1471-0528
pISSN - 1470-0328
DOI - 10.1046/j.1471-0528.2003.00023.x
Subject(s) - medicine , endocrinology , myosin light chain kinase , contractility , receptor , myosin , biology , phospholipase c , microbiology and biotechnology , chemistry
The mechanism of labour is not fully understood and further research into this important physiological process is needed. In some species, notably sheep, parturition is due to activation of the fetal hypothalamic–pituitary–adrenal axis. However, in primates, this axis appears to have a supportive, rather than essential role. Successful parturition requires an increase in coordinated uterine contractility together with changes in connective tissue that allow cervical ripening and dilatation. In most mammals, however, these changes are synchronised by a fall in maternal progesterone levels and a rise in oestrogens. This is not the case in women in whom the onset of labour occurs without apparent changes in circulating steroid levels. The basis of uterine contractility is the interaction between actin and myosin in myometrial smooth muscle cells. This is driven by calcium through Ca 2+ –calmodulin‐dependent myosin light chain kinase (MLCK) activity. Moreover, calcium sensitisation occurs via activation of Rho kinase, a calcium‐independent pathway that promotes contractility by inhibiting myosin phosphatase and probably by phosphorylating myosin on the same site as MLCK. Uterine activity can be modulated by many G‐protein coupled receptors (GPCRs). For example, receptors coupled to Gα q (oxytocin‐, prostanoid FP and TP, endothelin‐receptors) stimulate contractility by activating the phospholipase C/Ca 2+ pathway; receptors coupled to Gα s ( β 2 ‐adrenoceptors, prostanoid EP2 and IP, some 5‐hydroxytryptamine receptors e.g. 5‐HT 7 ) relax the uterus by increasing myometrial cyclic AMP levels; and receptors coupled to Gα i ( α 2 ‐adrenoceptors, muscarinic, 5‐HT 1 ) potentiate contractility, probably by inhibiting cAMP production. Because of its relative abundance in pregnant uterine tissue, the oxytocin receptor is an obvious target for tocolytic therapy. Oxytocin antagonists have been introduced into clinical practice for the management of preterm labour and offer the advantage of uterine selectivity and fewer side effects than conventional beta‐agonist therapy.