Mechanisms Underlying Oxytocin-Induced Excitation of Supraoptic Neurons: Prostaglandin Mediation of Actin Polymerization

Abstract

Wang, Yu-Feng and Glenn I. Hatton. Mechanisms underlying oxytocin-induced excitation of supraoptic neurons: prostaglandin mediation of actin polymerization. J Neurophysiol 95: 3933-3947, 2006. First published March 22, 2006 doi:10.1152/jn.01267.2005. In nonneuronal tissues, activation of oxytocin receptors (OTRs), like other G␣ q/11 type G-protein-coupled receptors (G␣ q/11 /GPCRs), increase prostaglandin (PG) expression. This is not known for the OTRs expressed by central OT neurons. We examined mechanisms underlying OT's effects on supraoptic nucleus (SON) OT and vasopressin (VP) neurons in hypothalamic slices from lactating rats. OT application (10 pM, 10 min) significantly increased firing rates of OT and VP neurons, both of which expressed OTRs. Indomethacin, an inhibitor of PG synthetases, blocked these increases. OTR (but not a V 1 receptor) antagonist blocked OT effects without blocking the excitatory effect of PGE 2 . Tetanus toxin blocked OT effects on fast synaptic inputs and firing activity of SON neurons but not OT-evoked depolarization, suggesting involvement of both pre-and postsynaptic neurons. Indomethacin also blocked the excitatory effects of phenylephrine, another G␣ q/11 /GPCR activating agent but not those of PGE 2 , a non-G␣ q/11 / GPCR activating agent in the SON. OT or phenylephrine, but not glutamate or KCl, enhanced cyclooxygenase 2 expression at cytosolic loci in SON neurons and nearby astrocytes, as revealed by immunocytochemistry. This OT effect was not blocked by TTX. Western blot analyses showed that OT significantly increased cyclooxygenase 2 but not actin expression. OT promoted the formation of filamentous actin (F-actin) networks at membrane subcortical areas of both OT and VP neurons. Indomethacin blocked enhancement of F-actin networks by OT but not by PGE 2 . These results indicate that PGs serve as a common mediator of G␣ q/11 /GPCR-activating agents in neuronal function.

Interaction of Extracellular Signal-Regulated Protein Kinase 1/2 with Actin Cytoskeleton in Supraoptic Oxytocin Neurons and Astrocytes: Role in Burst Firing

“…The brain slice and patch-clamp recording procedures were similar to those described in our previous reports (Wang and Hatton, 2006). Briefly, coronal brain slices, 300 m thick, containing the SON were obtained from Sprague Dawley (Holtzman strain) lactating rats (postpartum day 8 -13).…”

“…Another major target of OT actions is actin. OT can cause actin polymerization in OT neurons (Wang and Hatton, 2006) and its contraction in myoepithelium or myometrium (Gimpl and Fahrenholz, 2001). OT actions on actin are mediated by producing prostaglandins (Wang and Hatton, 2006), a key player in OT-evoked bursts (Hatton and Wang, 2005).…”

“…OT can cause actin polymerization in OT neurons (Wang and Hatton, 2006) and its contraction in myoepithelium or myometrium (Gimpl and Fahrenholz, 2001). OT actions on actin are mediated by producing prostaglandins (Wang and Hatton, 2006), a key player in OT-evoked bursts (Hatton and Wang, 2005). The production of prostaglandin also depends on ERK1/2 activation (Zhong et al, 2003;Reversi et al, 2005).…”

“…The production of prostaglandin also depends on ERK1/2 activation (Zhong et al, 2003;Reversi et al, 2005). Moreover, OTRs are expressed by both SON neurons and astrocytes (Wang and Hatton, 2006), which allows OT to mobilize various cells to actualize the milk-ejection reflex (MER). However, it remains a question in burst generation how pERK1/2 and actin interact among SON neurons and astrocytes.…”

An overview of the oxytocin-oxytocin receptor signaling network

“…OXT plays an important role in potentiating a response to a range of pro-social behaviors and in evoking contentment, inducing trust, generosity, and bonding in humans and other animals (Grillon et al 2013). Prostaglandins are mediators of OXT actions such as excitation in supraoptic nuclei of neurons released in response to OXTR agonists (Wang and Hatton 2006). Cardiac activity of OXT involves maintenance of blood pressure, increased angiogenesis and anti-inflammatory activity (Gutkowska and Jankowski 2012).…”