Tetanic Facilitation of Neuromuscular Transmission by Adenosine A(2A) and Muscarinic M-1 Receptors is Dependent on the Uptake of Choline via High-Affinity Transporters

• Tipo: Artigo em Revista Científica Internacional
• Data: 2019

Autores

Castellao Santana, LM (Autor) Outra; Abiko, PY (Autor) Outra; Ambiel, CR (Autor) Outra; Peixoto, AR (Autor) Outra; Noronha Matos, JB (Autor) ICBAS; Paulo Correia de Sá (Autor) ICBAS; Alves Do Prado, W (Autor) Outra

Revista

Título: Pharmacology

Vol. 103

Páginas: 38-49

ISSN: 0031-7012

Editora: Karger

Indexação

ISI Web of Knowledge - 0 Citações

Scopus - 0 Citações

Outras Informações

ID Authenticus: P-00P-TWW

DOI: 10.1159/000494058

Abstract (EN): Background/Aims: In this study, we evaluated the functional impact of facilitatory presynaptic adenosine A(2A) and muscarinic M-1 receptors in the recovery of neuromuscular tetanic depression caused by the blockage of high-affinity choline transporter (HChT) by hemicholinium-3 (HC-3), a condition that mimics a myasthenia-like condition. Methods: Rat diaphragm preparations were indirectly stimulated via the phrenic nerve trunk with 50-Hz frequency trains, each consisting of 500-750 supramaximal intensity pulses. The tension at the beginning (A) and at the end (B) of the tetanus was recorded and the ratio (R) B/A calculated. Results: Activation of A(2A) and M-1 receptors with CGS21680 (CGS; 2 nmol/L) and McN-A-343c (McN; 3 mu mol/L) increased R values. Similar facilitatory effects were obtained with forskolin (FSK; 3 mu mol/L) and phorbol 12-myristate 13-acetate (PMA; 10 mu mol/L), which activate adenylate cyclase and protein kinase C respectively. HC-3 (4 mu mol/L) decreased transmitter exocytosis measured by real-time videomicroscopy with the FM4-64 fluorescent dye and prevented the facilitation of neuromuscular transmission caused by CGS, McN, and FSK, with a minor effect on PMA. The acetylcholinesterase inhibitor, neostigmine (NEO; 0.5 mu mol/L), also decreased transmitter exocytosis. The paradoxical neuromuscular tetanic fade caused by NEO (0.5 mu mol/L) was also prevented by HC-3 (4 mu mol/L) and might result from the rundown of the positive feedback mechanism operated by neuronal nicotinic receptors (blocked by hexamethonium, 120 mu mol/L). Conclusion: Data suggest that the recovery of tetanic neuromuscular facilitation by adenosine A(2A) and M-1 receptors is highly dependent on HChT activity and may be weakened in myasthenic patients when HChT is inoperative. (C) 2018 S. Karger AG, Basel

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 12