{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,5,14]],"date-time":"2025-05-14T02:28:52Z","timestamp":1747189732403,"version":"3.40.5"},"reference-count":72,"publisher":"Canadian Science Publishing","issue":"8","license":[{"start":{"date-parts":[[2022,8,1]],"date-time":"2022-08-01T00:00:00Z","timestamp":1659312000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.nrcresearchpress.com\/page\/about\/CorporateTextAndDataMining"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Can. J. Physiol. Pharmacol."],"published-print":{"date-parts":[[2022,8,1]]},"abstract":"<jats:p> \u03b3-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<jats:sup>+<\/jats:sup> K<jats:sup>+<\/jats:sup> Cl<jats:sup>-<\/jats:sup> cotransporters (NKCC) and requires calcium influx. In the presence of guanethidine (3\u00a0\u00b5mol\/L), atropine (3\u00a0\u00b5mol\/L), and indomethacin (1\u00a0\u00b5mol\/L), relaxations induced by GABA (100\u00a0\u00b5mol\/L), KCl (5\u201310\u00a0mmol\/L) and electrical field stimulation (1\u20138\u00a0Hz, 2\u00a0ms, 60\u00a0V), but not those induced by bradykinin (10\u2013100\u00a0nmol\/L) were abolished by lidocaine (300\u00a0\u00b5mol\/L). However, only GABA-induced relaxations were reduced in a concentration-dependent manner by the NKCC1\/2 inhibitors bumetanide (0.1\u20131\u00a0\u00b5mol\/L) and furosemide (1\u201310\u00a0\u00b5mol\/L). GABA-induced NANC neuronal relaxation was abolished by bicuculline (30\u00a0\u00b5mol\/L) and inhibited by N-nitroarginine methyl ester (l-NAME, 300\u00a0\u00b5mol\/L). The \u03c9-conotoxin GVIA (1\u00a0\u00b5mol\/L), which acts exclusively on neuronal Ca<jats:sub>V<\/jats:sub>2 channels, but not on smooth muscle voltage-gated Ca<jats:sup>2+<\/jats:sup> Ca<jats:sub>V<\/jats:sub>1 channels, and nonselective blockers of these channels (verapamil 100\u00a0nmol\/L and ruthenium red 10\u00a0\u00b5mol\/L), reduced GABA-induced relaxations. These results showed that the activation of GABA<jats:sub>A<\/jats:sub> receptors induces NANC nitrergic neuronal relaxations in the rat duodenum, which depend on NKCC activity and Ca<jats:sub>V<\/jats:sub>2 channel activation, suggesting that this phenomenon results from neuronal depolarization promoted by Cl<jats:sup>\u2212<\/jats:sup> efflux through GABA<jats:sub>A<\/jats:sub> receptors, with subsequent Ca<jats:sup>2+<\/jats:sup> influx and nitric oxide release. <\/jats:p>","DOI":"10.1139\/cjpp-2021-0639","type":"journal-article","created":{"date-parts":[[2022,7,26]],"date-time":"2022-07-26T11:02:13Z","timestamp":1658833333000},"page":"728-740","source":"Crossref","is-referenced-by-count":0,"title":["Pharmacological evidence that GABA-induced relaxation of rat proximal duodenum longitudinal muscle depends on NKCC cotransporter activity and Ca<sup>2+<\/sup> influx"],"prefix":"10.1139","volume":"100","author":[{"given":"Francisco Chagas","family":"Filho","sequence":"first","affiliation":[{"name":"Biophysics and Physiology Department, 64049-550, Health Sciences Center, Federal University of Piau\u00ed, Teresina, Piau\u00ed, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Janyerson Dannys Pereira","family":"Silva","sequence":"additional","affiliation":[{"name":"Biophysics and Physiology Department, 64049-550, Health Sciences Center, Federal University of Piau\u00ed, Teresina, Piau\u00ed, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caio","family":"Petri","sequence":"additional","affiliation":[{"name":"Biophysics and Physiology Department, 64049-550, Health Sciences Center, Federal University of Piau\u00ed, Teresina, Piau\u00ed, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7393-2162","authenticated-orcid":false,"given":"Jo\u00e3o Santos 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