{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T14:31:02Z","timestamp":1769005862951,"version":"3.49.0"},"reference-count":0,"publisher":"S. Karger AG","issue":"1-2","license":[{"start":{"date-parts":[[2018,10,31]],"date-time":"2018-10-31T00:00:00Z","timestamp":1540944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"},{"start":{"date-parts":[[2018,10,31]],"date-time":"2018-10-31T00:00:00Z","timestamp":1540944000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.karger.com\/Services\/SiteLicenses"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmacology"],"published-print":{"date-parts":[[2019]]},"abstract":"<b><i>Background\/Aims:<\/i><\/b> In this study, we evaluated the functional impact of facilitatory presynaptic adenosine A<sub>2A<\/sub> and muscarinic M<sub>1<\/sub> 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. <b><i>Methods:<\/i><\/b> Rat diaphragm preparations were indirectly stimulated via the phrenic nerve trunk with 50-Hz frequency trains, each consisting of 500\u2013750 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. <b><i>Results:<\/i><\/b> Activation of A<sub>2A<\/sub> and M<sub>1<\/sub> receptors with CGS21680 (CGS; 2\u00a0nmol\/L) and McN-A-343c (McN; 3 \u03bcmol\/L) increased R values. Similar facilitatory effects were obtained with forskolin (FSK; 3 \u03bcmol\/L) and phorbol 12-myristate 13-acetate (PMA; 10 \u03bcmol\/L), which activate adenylate cyclase and protein kinase C respectively. HC-3 (4 \u03bcmol\/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 \u03bcmol\/L), also decreased transmitter exocytosis. The paradoxical neuromuscular tetanic fade caused by NEO (0.5 \u03bcmol\/L) was also prevented by HC-3 (4\u00a0\u03bcmol\/L) and might result from the rundown of the positive feedback mechanism operated by neuronal nicotinic receptors (blocked by hexamethonium, 120 \u03bcmol\/L). <b><i>Conclusion:<\/i><\/b> Data suggest that the recovery of tetanic neuromuscular facilitation by adenosine A<sub>2A<\/sub> and M<sub>1<\/sub> receptors is highly dependent on HChT activity and may be weakened in myasthenic patients when HChT is inoperative.<\/jats:p>","DOI":"10.1159\/000494058","type":"journal-article","created":{"date-parts":[[2018,10,31]],"date-time":"2018-10-31T22:02:53Z","timestamp":1541023373000},"page":"38-49","source":"Crossref","is-referenced-by-count":4,"title":["Tetanic Facilitation of Neuromuscular Transmission by Adenosine A<sub>2A<\/sub> and Muscarinic M<sub>1<\/sub> Receptors is Dependent on the Uptake of Choline via High-Affinity Transporters"],"prefix":"10.1159","volume":"103","author":[{"given":"Lilian\u00a0Martins","family":"Castell\u00e3o-Santana","sequence":"first","affiliation":[]},{"given":"Priscila","family":"Yumi\u00a0Abiko","sequence":"additional","affiliation":[]},{"given":"Celia\u00a0Regina","family":"Ambiel","sequence":"additional","affiliation":[]},{"given":"Ana\u00a0Rita","family":"Peixoto","sequence":"additional","affiliation":[]},{"given":"Jos\u00e9\u00a0Bernardo","family":"Noronha-Matos","sequence":"additional","affiliation":[]},{"given":"Paulo","family":"Correia-de-S\u00e1","sequence":"additional","affiliation":[]},{"given":"Wilson","family":"Alves-Do-Prado","sequence":"additional","affiliation":[]}],"member":"127","published-online":{"date-parts":[[2018,10,31]]},"container-title":["Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/494058","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.karger.com\/Article\/Pdf\/494058","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,23]],"date-time":"2025-04-23T17:00:22Z","timestamp":1745427622000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/000494058"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,10,31]]},"references-count":0,"journal-issue":{"issue":"1-2","published-online":{"date-parts":[[2019,2,8]]}},"URL":"https:\/\/doi.org\/10.1159\/000494058","archive":["Portico"],"relation":{},"ISSN":["0031-7012","1423-0313"],"issn-type":[{"value":"0031-7012","type":"print"},{"value":"1423-0313","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,10,31]]}}}