Age-Dependent Effects of Oxytocin and Oxytocin Receptor Antagonists on Bladder Contractions: Implications for the Treatment of Overactive Bladder Syndrome
Overactive bladder (OAB) is an age-related disorder characterised by unstable bladder contractions resulting in disruptive lower urinary tract symptoms (LUTS), thus creating a profound impact on an individual’s quality of life. The development of LUTS may be linked to the overexpression of oxytocin...
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| Format: | Article |
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MDPI AG
2024-03-01
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| Series: | Biomedicines |
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| Online Access: | https://www.mdpi.com/2227-9059/12/3/674 |
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| author | Masroor Badshah Jibriil Ibrahim Nguok Su Penny Whiley Ralf Middendorff Michael Whittaker Betty Exintaris |
| author_facet | Masroor Badshah Jibriil Ibrahim Nguok Su Penny Whiley Ralf Middendorff Michael Whittaker Betty Exintaris |
| author_sort | Masroor Badshah |
| collection | DOAJ |
| description | Overactive bladder (OAB) is an age-related disorder characterised by unstable bladder contractions resulting in disruptive lower urinary tract symptoms (LUTS), thus creating a profound impact on an individual’s quality of life. The development of LUTS may be linked to the overexpression of oxytocin receptors (OXTRs) within the bladder detrusor muscle, resulting in increased baseline myogenic tone. Thus, it is hypothesised that targeting OXTRs within the bladder using oxytocin antagonists may attenuate myogenic tone within the bladder, thereby providing a new therapeutic avenue for treating OAB. Organ bath contractility and immunohistochemistry techniques were conducted on bladder tissue sourced from young rats (7–8 weeks and 10–12 weeks) and older rats (4–5 months and 7–9 months). Organ bath studies revealed that oxytocin (OT) significantly increased bladder contractions, which were significantly attenuated by [β-Mercapto-β,β-cyclopentamethylenepropionyl1, O-Me-Tyr2, Orn8]-Oxytocin) (1 µM) (**** <i>p</i> < 0.0001) and atosiban (10 µM) in both young and older rats (** <i>p</i> < 0.01); in contrast, cligosiban (1 µM and 10 µM) did not inhibit OT-induced contractions in both young and older rats (<i>p</i> ≥ 0.05). Interestingly, cligosiban (1 µM and 10 µM) significantly reduced the frequency of spontaneous contractions within the bladder of both young (*** <i>p</i> < 0.001) and older rats (**** <i>p</i> < 0.0001), while atosiban (10 µM) only demonstrated this effect in older rats (** <i>p</i> < 0.01). Furthermore, immunohistochemistry (IHC) analysis revealed significant colocalization of nuclear-specific oxytocin receptors (OXTRs) in the contractile (smooth muscle) cells within young (** <i>p</i> < 0.01) and older rats (* <i>p</i> < 0.05), indicating OT may be a key modulator of bladder contractility. |
| first_indexed | 2024-04-24T18:31:00Z |
| format | Article |
| id | doaj.art-3401b4361d9e43e5840a0623975f7863 |
| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-04-24T18:31:00Z |
| publishDate | 2024-03-01 |
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| record_format | Article |
| series | Biomedicines |
| spelling | doaj.art-3401b4361d9e43e5840a0623975f78632024-03-27T13:23:06ZengMDPI AGBiomedicines2227-90592024-03-0112367410.3390/biomedicines12030674Age-Dependent Effects of Oxytocin and Oxytocin Receptor Antagonists on Bladder Contractions: Implications for the Treatment of Overactive Bladder SyndromeMasroor Badshah0Jibriil Ibrahim1Nguok Su2Penny Whiley3Ralf Middendorff4Michael Whittaker5Betty Exintaris6Hudson Institute of Medical Research, Monash University, Clayton, VIC 3168, AustraliaMonash Institute of Pharmaceutical Sciences, Parkville, VIC 3052, AustraliaMonash Institute of Pharmaceutical Sciences, Parkville, VIC 3052, AustraliaHudson Institute of Medical Research, Monash University, Clayton, VIC 3168, AustraliaInstitute of Anatomy and Cell Biology, Justus-Liebig-University, 35390 Giessen, GermanyMonash Institute of Pharmaceutical Sciences, Parkville, VIC 3052, AustraliaMonash Institute of Pharmaceutical Sciences, Parkville, VIC 3052, AustraliaOveractive bladder (OAB) is an age-related disorder characterised by unstable bladder contractions resulting in disruptive lower urinary tract symptoms (LUTS), thus creating a profound impact on an individual’s quality of life. The development of LUTS may be linked to the overexpression of oxytocin receptors (OXTRs) within the bladder detrusor muscle, resulting in increased baseline myogenic tone. Thus, it is hypothesised that targeting OXTRs within the bladder using oxytocin antagonists may attenuate myogenic tone within the bladder, thereby providing a new therapeutic avenue for treating OAB. Organ bath contractility and immunohistochemistry techniques were conducted on bladder tissue sourced from young rats (7–8 weeks and 10–12 weeks) and older rats (4–5 months and 7–9 months). Organ bath studies revealed that oxytocin (OT) significantly increased bladder contractions, which were significantly attenuated by [β-Mercapto-β,β-cyclopentamethylenepropionyl1, O-Me-Tyr2, Orn8]-Oxytocin) (1 µM) (**** <i>p</i> < 0.0001) and atosiban (10 µM) in both young and older rats (** <i>p</i> < 0.01); in contrast, cligosiban (1 µM and 10 µM) did not inhibit OT-induced contractions in both young and older rats (<i>p</i> ≥ 0.05). Interestingly, cligosiban (1 µM and 10 µM) significantly reduced the frequency of spontaneous contractions within the bladder of both young (*** <i>p</i> < 0.001) and older rats (**** <i>p</i> < 0.0001), while atosiban (10 µM) only demonstrated this effect in older rats (** <i>p</i> < 0.01). Furthermore, immunohistochemistry (IHC) analysis revealed significant colocalization of nuclear-specific oxytocin receptors (OXTRs) in the contractile (smooth muscle) cells within young (** <i>p</i> < 0.01) and older rats (* <i>p</i> < 0.05), indicating OT may be a key modulator of bladder contractility.https://www.mdpi.com/2227-9059/12/3/674overactive bladderlower urinary tract symptomsoxytocinoxytocin receptor antagonist |
| spellingShingle | Masroor Badshah Jibriil Ibrahim Nguok Su Penny Whiley Ralf Middendorff Michael Whittaker Betty Exintaris Age-Dependent Effects of Oxytocin and Oxytocin Receptor Antagonists on Bladder Contractions: Implications for the Treatment of Overactive Bladder Syndrome Biomedicines overactive bladder lower urinary tract symptoms oxytocin oxytocin receptor antagonist |
| title | Age-Dependent Effects of Oxytocin and Oxytocin Receptor Antagonists on Bladder Contractions: Implications for the Treatment of Overactive Bladder Syndrome |
| title_full | Age-Dependent Effects of Oxytocin and Oxytocin Receptor Antagonists on Bladder Contractions: Implications for the Treatment of Overactive Bladder Syndrome |
| title_fullStr | Age-Dependent Effects of Oxytocin and Oxytocin Receptor Antagonists on Bladder Contractions: Implications for the Treatment of Overactive Bladder Syndrome |
| title_full_unstemmed | Age-Dependent Effects of Oxytocin and Oxytocin Receptor Antagonists on Bladder Contractions: Implications for the Treatment of Overactive Bladder Syndrome |
| title_short | Age-Dependent Effects of Oxytocin and Oxytocin Receptor Antagonists on Bladder Contractions: Implications for the Treatment of Overactive Bladder Syndrome |
| title_sort | age dependent effects of oxytocin and oxytocin receptor antagonists on bladder contractions implications for the treatment of overactive bladder syndrome |
| topic | overactive bladder lower urinary tract symptoms oxytocin oxytocin receptor antagonist |
| url | https://www.mdpi.com/2227-9059/12/3/674 |
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