Inhibition of PDE‐4 isoenzyme attenuates frequency and overall contractility of agonist‐evoked ureteral phasic contractions
Abstract The aim of this study was to investigate the functional role of phosphodiesterase enzymes (PDE) in the isolated porcine ureter. Distal ureteral strips were mounted in organ baths and pre‐contracted with 5‐HT (100 μM). Upon generation of stable phasic contractions, PDE‐4 and PDE‐5 inhibitors...
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| Format: | Article |
| Language: | English |
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Wiley
2024-02-01
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| Series: | Pharmacology Research & Perspectives |
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| Online Access: | https://doi.org/10.1002/prp2.1175 |
| _version_ | 1797305079058923520 |
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| author | Iris Lim Taishi Masutani Hikaru Hashitani Russ Chess‐Williams Donna Sellers |
| author_facet | Iris Lim Taishi Masutani Hikaru Hashitani Russ Chess‐Williams Donna Sellers |
| author_sort | Iris Lim |
| collection | DOAJ |
| description | Abstract The aim of this study was to investigate the functional role of phosphodiesterase enzymes (PDE) in the isolated porcine ureter. Distal ureteral strips were mounted in organ baths and pre‐contracted with 5‐HT (100 μM). Upon generation of stable phasic contractions, PDE‐4 and PDE‐5 inhibitors were added cumulatively to separate tissues. PDE‐4 inhibitors, such as rolipram (10 nM and greater) and roflumilast (100 nM and greater), resulted in significant attenuation of ureteral contractile responses, while a higher concentration of piclamilast (1 μM and greater) was required to induce a significant depressant effect. The attenuation effect by rolipram was abolished by SQ22536 (100 μM). PDE‐5 inhibitors, such as sildenafil and tadalafil, were not nearly as effective and were only able to suppress the 5‐HT‐induced contractions at higher concentrations of 1 μM. Rolipram significantly enhanced the depressant effect of forskolin, while sodium nitroprusside‐induced attenuation of contractile responses remained unchanged in the presence of tadalafil. In summary, our study demonstrates that PDE‐4 inhibitors are effective in attenuating 5‐HT‐induced contractility in porcine distal ureteral tissues, while PDE‐5 inhibitors are less effective. These findings suggest that PDE‐4 inhibitors, such as rolipram, may hold promise as potential therapeutic agents for the treatment of ureteral disorders attributable to increased intra‐ureteral pressure. |
| first_indexed | 2024-03-08T00:20:41Z |
| format | Article |
| id | doaj.art-1fba7bf45bc64cf8bf25111a1b61fb98 |
| institution | Directory Open Access Journal |
| issn | 2052-1707 |
| language | English |
| last_indexed | 2024-03-08T00:20:41Z |
| publishDate | 2024-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Pharmacology Research & Perspectives |
| spelling | doaj.art-1fba7bf45bc64cf8bf25111a1b61fb982024-02-16T09:36:32ZengWileyPharmacology Research & Perspectives2052-17072024-02-01121n/an/a10.1002/prp2.1175Inhibition of PDE‐4 isoenzyme attenuates frequency and overall contractility of agonist‐evoked ureteral phasic contractionsIris Lim0Taishi Masutani1Hikaru Hashitani2Russ Chess‐Williams3Donna Sellers4Centre for Urology, Faculty of Health Sciences & Medicine Bond University Gold Coast Queensland AustraliaDepartment of Cell Physiology Nagoya City University Graduate School of Medical Sciences Nagoya JapanDepartment of Cell Physiology Nagoya City University Graduate School of Medical Sciences Nagoya JapanCentre for Urology, Faculty of Health Sciences & Medicine Bond University Gold Coast Queensland AustraliaDepartment of Cell Physiology Nagoya City University Graduate School of Medical Sciences Nagoya JapanAbstract The aim of this study was to investigate the functional role of phosphodiesterase enzymes (PDE) in the isolated porcine ureter. Distal ureteral strips were mounted in organ baths and pre‐contracted with 5‐HT (100 μM). Upon generation of stable phasic contractions, PDE‐4 and PDE‐5 inhibitors were added cumulatively to separate tissues. PDE‐4 inhibitors, such as rolipram (10 nM and greater) and roflumilast (100 nM and greater), resulted in significant attenuation of ureteral contractile responses, while a higher concentration of piclamilast (1 μM and greater) was required to induce a significant depressant effect. The attenuation effect by rolipram was abolished by SQ22536 (100 μM). PDE‐5 inhibitors, such as sildenafil and tadalafil, were not nearly as effective and were only able to suppress the 5‐HT‐induced contractions at higher concentrations of 1 μM. Rolipram significantly enhanced the depressant effect of forskolin, while sodium nitroprusside‐induced attenuation of contractile responses remained unchanged in the presence of tadalafil. In summary, our study demonstrates that PDE‐4 inhibitors are effective in attenuating 5‐HT‐induced contractility in porcine distal ureteral tissues, while PDE‐5 inhibitors are less effective. These findings suggest that PDE‐4 inhibitors, such as rolipram, may hold promise as potential therapeutic agents for the treatment of ureteral disorders attributable to increased intra‐ureteral pressure.https://doi.org/10.1002/prp2.1175phasic contractionsphosphodiesterasephosphodiesterase inhibitorsroflumilastrolipramsildenafil |
| spellingShingle | Iris Lim Taishi Masutani Hikaru Hashitani Russ Chess‐Williams Donna Sellers Inhibition of PDE‐4 isoenzyme attenuates frequency and overall contractility of agonist‐evoked ureteral phasic contractions Pharmacology Research & Perspectives phasic contractions phosphodiesterase phosphodiesterase inhibitors roflumilast rolipram sildenafil |
| title | Inhibition of PDE‐4 isoenzyme attenuates frequency and overall contractility of agonist‐evoked ureteral phasic contractions |
| title_full | Inhibition of PDE‐4 isoenzyme attenuates frequency and overall contractility of agonist‐evoked ureteral phasic contractions |
| title_fullStr | Inhibition of PDE‐4 isoenzyme attenuates frequency and overall contractility of agonist‐evoked ureteral phasic contractions |
| title_full_unstemmed | Inhibition of PDE‐4 isoenzyme attenuates frequency and overall contractility of agonist‐evoked ureteral phasic contractions |
| title_short | Inhibition of PDE‐4 isoenzyme attenuates frequency and overall contractility of agonist‐evoked ureteral phasic contractions |
| title_sort | inhibition of pde 4 isoenzyme attenuates frequency and overall contractility of agonist evoked ureteral phasic contractions |
| topic | phasic contractions phosphodiesterase phosphodiesterase inhibitors roflumilast rolipram sildenafil |
| url | https://doi.org/10.1002/prp2.1175 |
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