Pharmacological evidence that GABA-induced relaxation of rat proximal duodenum longitudinal muscle depends on NKCC cotransporter activity and Ca2+ influx

Autor(es)

Chagas Filho, Francisco ; Silva, Janyerson Dannys Pereira ; Petri, Caio ; Almendra, Joao Santos Lima ; de Sousa, Icaro Araujo ; Cavalcanti, Suzana Maria Galvao ; Silva, Bagnolia A. ; Melo, Margareth Fatima Formiga ; Cavalcanti, Paulo Marques da Silva

• Tipo de documento: Artigo Científico
• Fonte: Canadian Journal of Physiology and Pharmacology; v. N/A, p. 13-pg., 2022-07-26.

Resumo

gamma-Aminobutyric acid (GABA) is the main inhibitory neurotransmitter in adult central nervous system (CNS) synapses, but it excites immature CNS neurons as well as neurons in the myenteric plexus. The present work aimed to determine whether GABA-induced nonadrenergic, noncholinergic (NANC) neuronal-mediated relaxation of the rat duodenum is dependent on the activity of Na+ K+ Cl- cotransporters (NKCC) and requires calcium influx. In the presence of guanethidine (3 mu mol/L), atropine (3 mu mol/L), and indomethacin (1 mu mol/L), relaxations induced by GABA (100 mu mol/L), KCl (5-10 mmol/L) and electrical field stimulation (1-8 Hz, 2 ms, 60 V), but not those induced by bradykinin (10-100 nmol/L) were abolished by lidocaine (300 mu mol/L). However, only GABA-induced relaxations were reduced in a concentration-dependent manner by the NKCC1/2 inhibitors bumetanide (0.1-1 mu mol/L) and furosemide (1-10 mu mol/L). GABA-induced NANC neuronal relaxationwas abolished by bicuculline (30 mu mol/L) and inhibited by N-nitroarginine methyl ester (l-NAME, 300 mu mol/L). The omega-conotoxin GVIA (1 mu mol/L), which acts exclusively on neuronal Ca(V)2 channels, but not on smooth muscle voltage-gated Ca2+ Ca(V)1 channels, and nonselective blockers of these channels (verapamil 100 nmol/L and ruthenium red 10 mu mol/L), reduced GABA-induced relaxations. These results showed that the activation of GABA(A) receptors induces NANC nitrergic neuronal relaxations in the rat duodenum, which depend on NKCC activity and Ca(V)2 channel activation, suggesting that this phenomenon results from neuronal depolarization promoted by Cl- efflux through GABA(A) receptors, with subsequent Ca2+ influx and nitric oxide release. (AU)

• Processo FAPESP: 97/14208-8 - Diferenças sexuais no desenvolvimento e nas alterações vasculares funcionais da hipertensão induzida por desoxicorticosterona e salina (DOCA-sal)
• Beneficiário: Rita de Cassia Aleixo Tostes Passaglia
• Modalidade de apoio: Auxílio à Pesquisa - Regular