Purinergic P2 receptors in the paraventricular nucleus of the hypothalamus are involved in hyperosmotic-induced sympathoexcitation

Purinergic P2 and glutamate NMDA receptor coupling contributes to osmotically driven excitability in hypothalamic magnocellular neurosecretory neurons

“…2011; Ferreira‐Neto et al . 2017) have shown that from all these subtypes, P2X 1 –P2X 7 and P2Y 1 , P2Y 2 and P2Y 12 are found to be present in the SON. Additionally, it has been shown that ATP exogenously applied or endogenously released can induce VP and OT release from hypothalamo‐neurohypophyseal system explants (Kapoor & Sladek, 2000; Song & Sladek, 2006; Song et al .…”

“…The ionotropic P2X receptor family consists of seven different isoforms (P2X 1 -P2X 7 ), while the metabotropic P2Y receptor family is composed of eight different isoforms described so far (P2Y 1 , P2Y 2 , P2Y 4 , P2Y 6 , P2Y 11 , P2Y 12 , P2Y 13 and P2Y 14 ) (Burnstock, 2020). Several studies based on different approaches, including PCR, western blot, immunohistochemistry and pharmacology (Yao et al 2003;Song et al 2011;Vavra et al 2011;Ferreira-Neto et al 2017) have shown that from all these subtypes, P2X 1 -P2X 7 and P2Y 1 , P2Y 2 and P2Y 12 are found to be present in the SON. Additionally, it has been shown that ATP exogenously applied or endogenously released can induce VP and OT release from hypothalamo-neurohypophyseal system explants (Kapoor & Sladek, 2000;Song et al , 2007, revealing an important neuroendocrine physiological role for ATP.…”

“…Moreover, we showed that this action, as well as an osmotically driven sympathoexcitation in the PVN involved a signalling coupling between P2 and non‐NMDA (AMPA) receptors (Ferreira‐Neto et al . 2013, 2015, 2017). Given that both purinergic and glutamatergic neurotransmission also regulate the activity of MNNs (Day et al .…”

To Inhibit or Enhance? Is There a Benefit to Positive Allosteric Modulation of P2X Receptors?

“…The hypothalamus also controls feeding and drinking behavior, reproductive behavior, and temperature regulation and P2X2 is expressed on neurons involved in the regulation of food intake (Collden et al, 2010). Other than regulating hormone secretion directly, P2X2 can play a neuromodulatory role by regulating the release of other neurotransmitters such as glutamate and GABA (Vavra et al, 2011) and in paraventricular neurons, P2X2 can modulate sympathetic activity (Ferreira-Neto et al, 2017). From a therapeutic viewpoint, disorders of the hypothalamus and pituitary gland typically include over-activation (e.g., Cushing's disease, tumors of NET) rather than under-activation and strategies are needed to limit excessive hormonal secretion.…”

Estudo dos mecanismos neuronais hipotalâmicos e bulbares envolvidos no modelo de hipertensão induzida por sobrecarga de sódio.

“…A inibição dos receptores purinérgicos P2 reduz a simpatoexcitação lombar e a potencialização das correntes excitatórias glutamatérgicas, provocadas pela hiperosmolaridade, nos NPC com projeções para o RVLM Ferreira-Neto et al, 2017). Já a VP, cuja liberação em resposta ao aumento da osmolaridade plasmática também se dá no próprio PVN (Ludwig et al, 1994;Ludwig & Leng, 2006), é capaz de ativar os NPC contribuindo para o desenvolvimento da resposta simpatoexcitatória observada tanto em modelos de desafio hiperosmotico agudo quanto crônico (Son et al 2013;Ribeiro et al, 2015).…”