skip to main content
Idioma:
Primo Search
Clear Search Box
Search in: Busca Geral
Busca Avançada
Busca por Índices

Protein kinase Cδ constrains the S-pathway to phrenic motor facilitation elicited by spinal 5-HT 7 receptors or severe acute intermittent hypoxia

Perim, Raphael R ; Fields, Daryl P ; Mitchell, Gordon S

The Journal of physiology, 2019-01, Vol.597 (2), p.481-498 [Periódico revisado por pares]

England

Texto completo disponível

Citações Citado por
  • Título:
    Protein kinase Cδ constrains the S-pathway to phrenic motor facilitation elicited by spinal 5-HT 7 receptors or severe acute intermittent hypoxia
  • Autor: Perim, Raphael R ; Fields, Daryl P ; Mitchell, Gordon S
  • Assuntos: Amphetamines - pharmacology ; Animals ; Cyclic AMP-Dependent Protein Kinases - antagonists & inhibitors ; Cyclic AMP-Dependent Protein Kinases - physiology ; Hypoxia - physiopathology ; Male ; Phrenic Nerve - physiology ; Protein Kinase C-delta - antagonists & inhibitors ; Protein Kinase C-delta - physiology ; Pyrazoles - pharmacology ; Rats, Sprague-Dawley ; Receptor, Serotonin, 5-HT2A - physiology ; Receptors, Serotonin - physiology ; Serotonin Receptor Agonists - pharmacology ; Spinal Cord - physiology ; Tetrahydronaphthalenes - pharmacology
  • É parte de: The Journal of physiology, 2019-01, Vol.597 (2), p.481-498
  • Descrição: Concurrent 5-HT (Q pathway) and 5-HT (S pathway) serotonin receptor activation cancels phrenic motor facilitation due to mutual cross-talk inhibition. Spinal protein kinase Cδ (PKCδ) or protein kinase A inhibition restores phrenic motor facilitation with concurrent Q and S pathway activation, demonstrating a key role for these kinases in cross-talk inhibition. Spinal PKCδ inhibition enhances adenosine-dependent severe acute intermittent hypoxia-induced phrenic long-term facilitation (S pathway), consistent with relief of cross-talk inhibition. Intermittent spinal serotonin receptor activation elicits long-lasting phrenic motor facilitation (pMF), a form of respiratory motor plasticity. When activated alone, spinal Gq protein-coupled serotonin 2A receptors (5-HT ) initiate pMF by a mechanism that requires ERK-MAP kinase signalling and new BDNF protein synthesis (Q pathway). Spinal Gs protein-coupled serotonin 7 (5-HT ) and adenosine 2A (A ) receptor activation also elicits pMF, but via distinct mechanisms (S pathway) that require Akt signalling and new TrkB protein synthesis. Although studies have shown inhibitory cross-talk interactions between these competing pathways, the underlying cellular mechanisms are unknown. We propose the following hypotheses: (1) concurrent 5-HT and 5-HT activation undermines pMF; (2) protein kinase A (PKA) and (3) NADPH oxidase mediate inhibitory interactions between Q (5-HT ) and S (5-HT ) pathways. Selective 5-HT (DOI hydrochloride) and 5HT (AS-19) agonists were administered intrathecally at C4 (three injections, 5-min intervals) in anaesthetized, vagotomized and ventilated male rats. With either spinal 5-HT or 5-HT activation alone, phrenic amplitude progressively increased (pMF). In contrast, concurrent 5-HT and 5-HT activation failed to elicit pMF. The 5-HT -induced Q pathway was restored by inhibiting PKA activity (Rp-8-Br-cAMPS). NADPH oxidase inhibition did not prevent cross-talk inhibition. Therefore, we investigated alternative mechanisms to explain Q to S pathway inhibition. Spinal protein kinase C (PKC) inhibition with Gö6983 or PKCδ peptide inhibitor restored the 5-HT -induced S pathway to pMF, revealing PKCδ as the relevant isoform. Spinal PKCδ inhibition enhanced the S pathway-dependent form of pMF elicited by severe acute intermittent hypoxia. We suggest that powerful constraints between 5-HT and 5-HT or A receptor-induced pMF are mediated by PKCδ and PKA, respectively.
  • Editor: England
  • Idioma: Inglês
Links
Voltar para lista de resultados

  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

Buscando em bases de dados remotas. Favor aguardar.