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© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.

Abstract

Indomethacin, ibuprofen, and acetylsalicylic acid (ASA) are non-steroidal anti-inflammatory drugs (NSAIDs) that inhibit prostaglandin (PG) synthesis. Previous studies in airway smooth muscle demonstrated that chronic exposure to testosterone (TES, 40 nM) enhances the relaxation induced by salbutamol and theophylline due to K+ channel increment, without modifying cyclooxygenase expression. This study examines how indomethacin, ibuprofen, and ASA affect K+ currents and the relaxation response to these bronchodilators. In organ baths, tracheas from young male guinea pigs chronically (48 h) treated with 40 nM TES showed increased relaxation to salbutamol and theophylline, which was completely abolished by indomethacin. Patch-clamp recordings revealed that TES increased salbutamol- and theophylline-induced K+ currents, and only indomethacin fully inhibited this potentiation; ibuprofen and ASA had partial effects. The involved currents included voltage-dependent K+ (KV) and high-conductance Ca2+-activated K+ (BKCa) channels. Our results demonstrate that indomethacin exerts a dual action, inhibiting K+ channel activity and PG synthesis, unlike ibuprofen and ASA. This dual mechanism explains its stronger inhibitory effect on TES-enhanced ASM relaxation. These findings suggest that indomethacin may counteract the protective effects of TES, which promotes anti-inflammatory and smooth muscle-relaxing states. Therefore, it is advisable to exercise caution when prescribing indomethacin to young males with asthma, as the protective role of TES may diminish, potentially resulting in an exacerbation of asthma symptoms.

Details

Title
Indomethacin Abolishes the Potentiation Effect of Testosterone on the Relaxation Induced by Salbutamol and Theophylline by Directly Blocking the K+ Channels in Airway Smooth Muscle
Author
Reyes-García, Jorge 1   VIAFID ORCID Logo  ; Carbajal-García Abril 1   VIAFID ORCID Logo  ; Díaz-Hernández Verónica 2   VIAFID ORCID Logo  ; Casas-Hernández, María F 1 ; Montaño, Luis M 1   VIAFID ORCID Logo 

 Departamento de Farmacología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico; [email protected] (J.R.-G.); [email protected] (A.C.-G.); 
 Departamento de Embriología, Facultad de Medicina, Universidad Nacional Autónoma de México, Mexico City 04510, Mexico 
First page
2259
Publication year
2025
Publication date
2025
Publisher
MDPI AG
e-ISSN
14203049
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
3217742615
Copyright
© 2025 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.