SUCKLING-INDUCED BURST DISCHARGES OF SUPRAOPTIC OXYTOCIN NEURONS IN RATS: PROSTAGLANDIN MEDIATION OF OXYTOCIN ACTIONS

Pulsatile release of hormones and neurotransmitters is widespread in mammals and typical of oxytocin secretion during lactation. Suckling-evoked pulsatile release of oxytocin follows a transient activation of hypothalamic oxytocin neurons in a burst-like firing pattern and leads to a bolus release of oxytocin and milk ejections. Prostaglandin (PG), a non-hormonal messenger cytokine, has been implicated in the activation of oxytocin neurons. To clarify the role of PGs in the activation of oxytocin neurons, we made the following observations. In patch-clamp recordings of oxytocin neurons in the supraoptic nucleus of brain slices from lactating rats, bath application of PGE2 evoked a significantly higher incidence of bursts than oxytocin did. Indomethacin, an inhibitor of PG synthesis, totally blocked oxytocin- but not PGE2-evoked bursts. Moreover, suckling-induced milk ejections and increased molecular association between extracellular signal-regulated protein kinase (ERK) 1/2 and actin were blocked by intracerebroventricular application of indomethacin. Intracerebroventricular administration of PD98059, a blocker of ERK 1/2 phosphorylation/activation, also blocked suckling-induced cyclooxygenase 2 (Cox-2, a PG synthetase) in oxytocin neurons and suckling-increased molecular association between ERK 1/2 and Cox-2. These results indicate that PGs are essential signaling links in the suckling-evoked bursting of oxytocin neurons; however, to evoke full bursts, PGs need other signaling events downstream to oxytocin receptors. This finding highlights the mediator effect of PGs on oxytocin-evoked pulsatile oxytocin release, and provides a model of signaling process of hormonal actions and therapeutic target of hormone-related diseases.