Effect of Roflumilast in airways disorders via dual inhibition of phosphodiesterase and Ca2+-channel
The bronchodilator effects of Roflumilast “a selective phosphodiesterase type-4 (PDE4)” inhibitor studied in this experimental protocol. The spiral strips of isolated guinea-pig tracheal chains mounted in organ bath and maintained in Krebs solution ventilated with carbogen at 32 °C and in Ca++ restr...
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| Format: | Article |
| Language: | English |
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Elsevier
2020-06-01
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| Series: | Saudi Pharmaceutical Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S131901642030089X |
| _version_ | 1811273390817804288 |
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| author | Faisal Imam Najeeb Ur Rehman Mohd Nazam Ansari Wajhul Qamar Muhammad Afzal Khalid Saad Alharbi |
| author_facet | Faisal Imam Najeeb Ur Rehman Mohd Nazam Ansari Wajhul Qamar Muhammad Afzal Khalid Saad Alharbi |
| author_sort | Faisal Imam |
| collection | DOAJ |
| description | The bronchodilator effects of Roflumilast “a selective phosphodiesterase type-4 (PDE4)” inhibitor studied in this experimental protocol. The spiral strips of isolated guinea-pig tracheal chains mounted in organ bath and maintained in Krebs solution ventilated with carbogen at 32 °C and in Ca++ restricted krebs solution. PDE inhibitory activity was evaluated by recording dose response curves using inhibitory effect of isoprenaline on CCh induced contractions. For confirmation of PDE inhibition the intracellular cAMP levels were also estimated. Roflumilast resulted a sharp inhibition in contractile responses of carbachol (CCh, 1 µM) and K+ (80 mM) and the results were almost similar to verapamil. In Ca++ restricted Krebs solution, a rightward shift in the Ca++ response curves observed in the tracheal chain strips which were pretreated with Roflumilast (0.001–0.003 mg/mL) and the maximum response was suppressed, similarly as with verapamil. PDE inhibitory effect of Roflumilast evaluated by recording dose-dependent (0.03–0.1 mg/mL) responses, the isoprenaline-induced inhibitory dose response curves shifted leftward similar to papaverine (PDE inhibitor). Pretreatment with Roflumilast exhibited elevated intracellular cAMP levels in tracheal strips. Findings of the experiment conclude bronchodilatory influence of Roflumilast via PDE and Ca++ channel inhibition. Results of current experiment offers comprehensive mechanistic background of Roflumilast in future as therapeutic bronchodilator for hyperactive bronchial airway diseases. |
| first_indexed | 2024-04-12T22:58:16Z |
| format | Article |
| id | doaj.art-d25af44146514fe7851f6a6e34f8e60c |
| institution | Directory Open Access Journal |
| issn | 1319-0164 |
| language | English |
| last_indexed | 2024-04-12T22:58:16Z |
| publishDate | 2020-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Saudi Pharmaceutical Journal |
| spelling | doaj.art-d25af44146514fe7851f6a6e34f8e60c2022-12-22T03:13:07ZengElsevierSaudi Pharmaceutical Journal1319-01642020-06-01286698702Effect of Roflumilast in airways disorders via dual inhibition of phosphodiesterase and Ca2+-channelFaisal Imam0Najeeb Ur Rehman1Mohd Nazam Ansari2Wajhul Qamar3Muhammad Afzal4Khalid Saad Alharbi5Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia; Corresponding authors at: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box: 2457, Riyadh 11451, Saudi Arabia (F. Imam). Department of Pharmacology & Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia. (M.N. Ansari).Department of Pharmacology & Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi ArabiaDepartment of Pharmacology & Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia; Corresponding authors at: Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box: 2457, Riyadh 11451, Saudi Arabia (F. Imam). Department of Pharmacology & Toxicology, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia. (M.N. Ansari).Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia; Central Laboratory; Research Center, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi ArabiaDepartment of Pharmacology, College of Pharmacy, Jouf University, Sakakah 72341, Saudi ArabiaDepartment of Pharmacology, College of Pharmacy, Jouf University, Sakakah 72341, Saudi ArabiaThe bronchodilator effects of Roflumilast “a selective phosphodiesterase type-4 (PDE4)” inhibitor studied in this experimental protocol. The spiral strips of isolated guinea-pig tracheal chains mounted in organ bath and maintained in Krebs solution ventilated with carbogen at 32 °C and in Ca++ restricted krebs solution. PDE inhibitory activity was evaluated by recording dose response curves using inhibitory effect of isoprenaline on CCh induced contractions. For confirmation of PDE inhibition the intracellular cAMP levels were also estimated. Roflumilast resulted a sharp inhibition in contractile responses of carbachol (CCh, 1 µM) and K+ (80 mM) and the results were almost similar to verapamil. In Ca++ restricted Krebs solution, a rightward shift in the Ca++ response curves observed in the tracheal chain strips which were pretreated with Roflumilast (0.001–0.003 mg/mL) and the maximum response was suppressed, similarly as with verapamil. PDE inhibitory effect of Roflumilast evaluated by recording dose-dependent (0.03–0.1 mg/mL) responses, the isoprenaline-induced inhibitory dose response curves shifted leftward similar to papaverine (PDE inhibitor). Pretreatment with Roflumilast exhibited elevated intracellular cAMP levels in tracheal strips. Findings of the experiment conclude bronchodilatory influence of Roflumilast via PDE and Ca++ channel inhibition. Results of current experiment offers comprehensive mechanistic background of Roflumilast in future as therapeutic bronchodilator for hyperactive bronchial airway diseases.http://www.sciencedirect.com/science/article/pii/S131901642030089XRoflumilastBronchodilatationPapaverinePhosphodiesterase inhibitorCa++ channel blocker |
| spellingShingle | Faisal Imam Najeeb Ur Rehman Mohd Nazam Ansari Wajhul Qamar Muhammad Afzal Khalid Saad Alharbi Effect of Roflumilast in airways disorders via dual inhibition of phosphodiesterase and Ca2+-channel Saudi Pharmaceutical Journal Roflumilast Bronchodilatation Papaverine Phosphodiesterase inhibitor Ca++ channel blocker |
| title | Effect of Roflumilast in airways disorders via dual inhibition of phosphodiesterase and Ca2+-channel |
| title_full | Effect of Roflumilast in airways disorders via dual inhibition of phosphodiesterase and Ca2+-channel |
| title_fullStr | Effect of Roflumilast in airways disorders via dual inhibition of phosphodiesterase and Ca2+-channel |
| title_full_unstemmed | Effect of Roflumilast in airways disorders via dual inhibition of phosphodiesterase and Ca2+-channel |
| title_short | Effect of Roflumilast in airways disorders via dual inhibition of phosphodiesterase and Ca2+-channel |
| title_sort | effect of roflumilast in airways disorders via dual inhibition of phosphodiesterase and ca2 channel |
| topic | Roflumilast Bronchodilatation Papaverine Phosphodiesterase inhibitor Ca++ channel blocker |
| url | http://www.sciencedirect.com/science/article/pii/S131901642030089X |
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