The exact mechanisms involved in the onset of parturition in humans remain unknown, and it is possible that labour occurs due to a loss of uterine quiescence, an induction of uterine contractility, or a combination of both. Elucidation of the pathways, and the factors, involved in parturition should ultimately assist in the anticipation, and prevention, of preterm labour. Preterm labour remains a major cause of perinatal mortality and morbidity, and whilst accounting for only 7 % of total deliveries is responsible for 70 % of perinatal deaths . Furthermore, whilst 50 % of preterm babies now survive, largely due to improvements in neonatal care, a wide range of both short-and long-term complications, including respiratory disease, intracerebral haemorrhage, and cerebral palsy, are associated with early preterm deliveries occurring before 32 weeks gestation (Keirse, 1995).
Myometrial contractilityThe major factor underlying contractility in myometrial smooth muscle is an increase in intracellular calcium levels due to both mobilisation of calcium from the sarcoplasmic reticulum (SR), and entry of extracellular calcium via receptor-and voltage-operated calcium channels (Word, 1995). Several hormones, including oxytocin, vasopressin, prostaglandin F 2a , and thromboxane A 2 , act upon receptors coupled to the phospholipase C (PLC) pathway. Activation of PLC generates two second messengers, 1,2-diacylglycerol, which stimulates protein kinase C (PKC), and inositol trisphosphate which mobilises calcium from the SR. Calcium, in combination with calmodulin activates the enzyme myosin light chain kinase (MLCK) bringing about the phosphorylation of the 20 kDa myosin light chain, the interaction of myosin with actin and, hence, contractility (Wray, 1993;L贸pez Bernal et al. 1997).
Myometrial quiescenceThroughout gestation it is vital that the uterus remains relatively quiescent permitting the fetus to grow and mature in preparation for extrauterine life. The second messenger cyclic AMP influences a wide range of physiological events including metabolic processes such as gluconeogenesis, secretory activity, learning, ion channel conductance and cytokine production. In addition, cAMP promotes the relaxation of myometrial, and other, smooth muscle cells via activation of cAMP-dependent protein kinase (PKA) (Fig. 1)