Role of AMPA and NMDA receptors on vasopressin and oxytocin secretion induced by hypertonic extracellular volume expansion

Abstract

Vasopressin (AVP) and oxytocin (OT) are essential for the control of extracellular fluid osmolality and volume. Secretion of these hormones is modulated by several mechanisms, including NMDA and AMPA L-glutamate receptors in magnocellular cells of paraventricular (PVN) and supraoptic (SON) hypothalamic nuclei. Thus, to better understand the participation of L-glutamate on the neuroendocrine control of AVP and OT, this work evaluated the effects of intracerebroventricular (icv) NMDA and AMPA receptor antagonists on plasma AVP and OT levels induced by extracellular volume expansion (EVE). Cannulated rats received icv NMDA (AP5) and AMPA (NBQX) antagonists in 10 and 30nmol/5μl/rat doses and were subjected to either isotonic (0.15 M NaCl, 2ml/100g) or hypertonic (0.30 M NaCl, 2ml/100g) EVE. Blood samples were collected for plasma AVP and OT determination. Isotonic EVE did not change plasma AVP and OT levels, but hypertonic EVE increased both AVP and OT plasma levels. AP5 reduced plasma AVP, but it did not change the OT level induced by hypertonic EVE. On the other hand, NBQX reduced plasma OT, but did not alter the AVP plasma level. Our data shows that L-glutamate controls the secretion of neurohypophyseal hormones through the NMDA receptor for AVP release, and through the AMPA receptor for OT release, both in response to hypertonic EVE. This article is protected by copyright. All rights reserved.

AMPA and angiotensin type 1 receptors are necessary for hemorrhage-induced vasopressin secretion

“…When in anesthetic plane, animals were placed in a stereotaxic apparatus. Next, a cannula (stainless steel; 0.7 mm external diameter, 0.4 mm internal diameter, and 10 mm long) was inserted into the right lateral ventricle at the coordinates: 0.5 mm posterior to bregma, 1.4 mm lateral from the middle line, 3.6 mm down from the skull, as previously described (13). All animals received a prophylactic dose of antibiotic (50,000 units of penicillin G, intramuscular).…”

“…Then, 20 min before hemorrhage, animals were submitted to icv microinjection of 5 mL/rat of vehicle (0.9% saline solution), NBQX (#1044, Tocris Cookson Ltd., United Kingdom), AP5 (#A8054, Sigma Chemical Co., USA), or losartan (Merck Sharp & Dohme, USA). Both NBQX and AP5 were used at doses of 10 and 30 nmol/5 mL per rat, as previously described (13).…”

“…The plasma was separated by centrifugation at 1600 g for 20 min at 4°C and then stored at -20°C until extraction. Plasma AVP concentration was measured by specific radioimmunoassay as previously described (13). Assay sensitivity and intra-and inter-assay coefficients of variation were 0.7 pg/mL, 7.6, and 12%, respectively.…”

“…In hypothalamusneurohypophysis explants, AMPA receptor antagonists block the AVP secretion in response to osmotic stimulation (11), whilst metabotropic glutamate receptors did not influence AVP release (12). We have recently shown that L-glutamate stimulates the secretion of AVP through NMDA receptors after hypertonic extracellular volume expansion (EVE) (13). The participation of different ionotropic L-glutamate receptors in hemorrhage-induced AVP release is not known.…”

P2X2 Receptor Expression and Function Is Upregulated in the Rat Supraoptic Nucleus Stimulated Through Refeeding After Fasting

“…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). These inputs, in particular those using glutamate (Decavel and Curras, 1997; Boudaba et al, 2003; Iremonger et al, 2010; Vilhena-Franco et al, 2018) and γ-aminobutyric acid (GABA) (Brussaard and Kits, 1999) as neurotransmitters, play an important role in the generation of the specific pattern of activity in AVP and OT neurons (Moos, 1995; Voisin et al, 1995; Jourdain et al, 1998; Brussaard and Kits, 1999; Israel et al, 2010; Choe et al, 2015).…”