{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T11:23:39Z","timestamp":1784805819501,"version":"3.55.0"},"reference-count":108,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,4,24]],"date-time":"2024-04-24T00:00:00Z","timestamp":1713916800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Direcci\u00f3n General de Asuntos del Personal Acad\u00e9mico (DGAPA), Universidad Nacional Aut\u00f3noma de M\u00e9xico","award":["IN200522"],"award-info":[{"award-number":["IN200522"]}]},{"name":"Direcci\u00f3n General de Asuntos del Personal Acad\u00e9mico (DGAPA), Universidad Nacional Aut\u00f3noma de M\u00e9xico","award":["IA201322"],"award-info":[{"award-number":["IA201322"]}]},{"name":"Direcci\u00f3n General de Asuntos del Personal Acad\u00e9mico (DGAPA), Universidad Nacional Aut\u00f3noma de M\u00e9xico","award":["IA203924"],"award-info":[{"award-number":["IA203924"]}]},{"name":"Direcci\u00f3n General de Asuntos del Personal Acad\u00e9mico (DGAPA), Universidad Nacional Aut\u00f3noma de M\u00e9xico","award":["IN200924"],"award-info":[{"award-number":["IN200924"]}]},{"name":"Direcci\u00f3n General de Asuntos del Personal Acad\u00e9mico (DGAPA), Universidad Nacional Aut\u00f3noma de M\u00e9xico","award":["CF\/2019-137725"],"award-info":[{"award-number":["CF\/2019-137725"]}]},{"name":"Direcci\u00f3n General de Asuntos del Personal Acad\u00e9mico (DGAPA), Universidad Nacional Aut\u00f3noma de M\u00e9xico","award":["CBF2023-24-1074"],"award-info":[{"award-number":["CBF2023-24-1074"]}]},{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda, M\u00e9xico","doi-asserted-by":"publisher","award":["IN200522"],"award-info":[{"award-number":["IN200522"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda, M\u00e9xico","doi-asserted-by":"publisher","award":["IA201322"],"award-info":[{"award-number":["IA201322"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda, M\u00e9xico","doi-asserted-by":"publisher","award":["IA203924"],"award-info":[{"award-number":["IA203924"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda, M\u00e9xico","doi-asserted-by":"publisher","award":["IN200924"],"award-info":[{"award-number":["IN200924"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda, M\u00e9xico","doi-asserted-by":"publisher","award":["CF\/2019-137725"],"award-info":[{"award-number":["CF\/2019-137725"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003141","name":"Consejo Nacional de Ciencia y Tecnolog\u00eda, M\u00e9xico","doi-asserted-by":"publisher","award":["CBF2023-24-1074"],"award-info":[{"award-number":["CBF2023-24-1074"]}],"id":[{"id":"10.13039\/501100003141","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Numerous studies suggest the involvement of adenosine-5\u2032-triphosphate (ATP) and similar nucleotides in the pathophysiology of asthma. Androgens, such as testosterone (TES), are proposed to alleviate asthma symptoms in young men. ATP and uridine-5\u2032-triphosphate (UTP) relax the airway smooth muscle (ASM) via purinergic P2Y2 and P2Y4 receptors and K+ channel opening. We previously demonstrated that TES increased the expression of voltage-dependent K+ (KV) channels in ASM. This study investigates how TES may potentiate ASM relaxation induced by ATP and UTP. Tracheal tissues treated with or without TES (control group) from young male guinea pigs were used. In organ baths, tracheas exposed to TES (40 nM for 48 h) showed enhanced ATP- and UTP-evoked relaxation. Tetraethylammonium, a K+ channel blocker, annulled this effect. Patch-clamp experiments in tracheal myocytes showed that TES also increased ATP- and UTP-induced K+ currents, and this effect was abolished with flutamide (an androgen receptor antagonist). KV channels were involved in this phenomenon, which was demonstrated by inhibition with 4-aminopyridine. RB2 (an antagonist of almost all P2Y receptors except for P2Y2), as well as N-ethylmaleimide and SQ 22,536 (inhibitors of G proteins and adenylyl cyclase, respectively), attenuated the enhancement of the K+ currents induced by TES. Immunofluorescence and immunohistochemistry studies revealed that TES did not modify the expression of P2Y4 receptors or COX-1 and COX-2, while we have demonstrated that this androgen augmented the expression of KV1.2 and KV1.5 channels in ASM. Thus, TES leads to the upregulation of P2Y4 signaling and KV channels in guinea pig ASM, enhancing ATP and UTP relaxation responses, which likely limits the severity of bronchospasm in young males.<\/jats:p>","DOI":"10.3390\/ijms25094652","type":"journal-article","created":{"date-parts":[[2024,4,25]],"date-time":"2024-04-25T08:08:32Z","timestamp":1714032512000},"page":"4652","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Testosterone Enhances KV Currents and Airway Smooth Muscle Relaxation Induced by ATP and UTP through P2Y4 Receptors and Adenylyl Cyclase Pathway"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1394-9971","authenticated-orcid":false,"given":"Abril","family":"Carbajal-Garc\u00eda","sequence":"first","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6226-7363","authenticated-orcid":false,"given":"Jorge","family":"Reyes-Garc\u00eda","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6119-3497","authenticated-orcid":false,"given":"Ver\u00f3nica","family":"D\u00edaz-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Departamento de Embriolog\u00eda, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda F.","family":"Casas-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco Javier","family":"Flores-Murrieta","sequence":"additional","affiliation":[{"name":"Unidad de Investigaci\u00f3n en Farmacolog\u00eda, Instituto Nacional de Enfermedades Respiratorias Ismael Cos\u00edo Villegas, Mexico City 14080, Mexico"},{"name":"Secci\u00f3n de Estudios de Posgrado e Investigaci\u00f3n, Escuela Superior de Medicina, Instituto Polit\u00e9cnico Nacional, Mexico City 11340, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0065-1298","authenticated-orcid":false,"given":"Luis M.","family":"Monta\u00f1o","sequence":"additional","affiliation":[{"name":"Departamento de Farmacolog\u00eda, Facultad de Medicina, Universidad Nacional Aut\u00f3noma de M\u00e9xico, Mexico City 04510, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,4,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"L466","DOI":"10.1152\/ajplung.00450.2020","article-title":"Blocking ATP-releasing channels prevents high extracellular ATP levels and airway hyperreactivity in an asthmatic mouse model","volume":"321","author":"Benavente","year":"2021","journal-title":"Am. 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