Abstract
Magnocellular neurons in the supraoptic nucleus (SON), which synthesize and release arginine vasopressin (AVP) and oxytocin (OT), express several subtypes of ATP-stimulated purinergic P2X receptors (P2XR) that modulate neuronal activity as well as neurotransmitter and hormone release. However, the physiological impact of this modulation is not well understood. Here, we tested a hypothesis that P2XRs play a role in the sustained release of hormones from SON neurons stimulated through fasting/refeeding. We studied the effect of 2 h of refeeding after 48 h of fasting on P2XR and P2YR mRNA expression and ATP-induced presynaptic and postsynaptic responses in the SON of 30-day-old rats. Quantitative real-time PCR revealed that the expression of P2X2R and AVP mRNA was upregulated, whereas P2X4R, P2X7R, P2Y2R, and OT mRNA levels were not significantly changed and P2Y1R mRNA expression was decreased. Whole-cell patch clamp recordings performed on isolated rat brain slices showed that the amplitude of the ATP-stimulated somatic current and the ATP-induced increases in the frequency of spontaneous GABAergic inhibitory postsynaptic currents were significantly higher in SON neurons from fasted/refed rats than in SON neurons from normally fed rats. No evidence was found for changes in the presynaptic effect of ATP in SON neurons not expressing somatic P2XRs. These results suggest that the increased activity of SON neurons synthesizing AVP is associated with enhanced expression of P2X2Rs on neuronal cell bodies and their GABAergic presynaptic nerve terminals.
Highlights
Mammalian magnocellular neurons in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) secrete either vasopressin (AVP) or oxytocin (OT) from their nerve terminals in the posterior pituitary in response to a variety of different physiological stimuli
Lucio-Oliveira et al, 2015) regulates P2X receptors (P2XR) gene expression in the SON, we performed quantitative PCR analysis with reverse transcription (RT-qPCR) to compare the mRNA expression of P2X2R, P2X4R, P2X7R, P2Y1R, and P2Y2R in SON tissue from 30-day-old rats refed for 2 h after 48 h of starvation with that in SON tissue isolated from controls, i.e., normally fed rats (Figure 1B)
Changes in the mRNA expression of OT, P2X4R, P2X7R, and P2Y2R were non-significant. These results showed that fasting/refeeding increases the expression of P2X2R and this effect correlates with the upregulation of arginine vasopressin (AVP) in the SON
Summary
Mammalian magnocellular neurons in the supraoptic nucleus (SON) and paraventricular nucleus (PVN) secrete either vasopressin (AVP) or oxytocin (OT) from their nerve terminals in the posterior pituitary in response to a variety of different physiological stimuli. AVP release increases as a function of plasma osmolality and water status of the body (Oliet and Bourque, 1993; Israel et al, 2010; Choe et al, 2015), whereas OT release is mainly caused by parturition and Purinergic Modulation of Neurotransmission in the SON suckling-induced reflex milk ejection (Moos, 1995; Voisin et al, 1995; Jourdain et al, 1998; Brussaard and Kits, 1999), These two peptides are locally released in various brain regions (Richard et al, 1991), including within the PVN and SON, where AVP and OT have local regulatory actions (Ludwig, 1998; Kombian et al, 2002; Leng and Ludwig, 2008) The secretion of both hormones is dependent on electrical activity of magnocellular neurons (Leng et al, 1999; Sladek and Kapoor, 2001; Armstrong, 2007; Li et al, 2007; Choe et al, 2015), which is under the control of various excitatory and inhibitory synaptic inputs (Hu and Bourque, 1991; Wuarin and Dudek, 1993; Shibuya et al, 2000; Israel et al, 2010). A higher incidence of GABA(A) receptor-mediated spontaneous inhibitory postsynaptic currents (sIPSCs) has been found in the SON neurons of pregnant rats than in those of virgin rats, consistent with the observations of an increase in the density of GABA-containing synaptic boutons (Brussaard and Kits, 1999)
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