Journal article
Authors list: Badshah, Masroor; Ibrahim, Jibriil; Su, Nguok; Whiley, Penny; Middendorff, Ralf; Whittaker, Michael; Exintaris, Betty
Publication year: 2024
Journal: Biomedicines
Volume number: 12
Issue number: 3
eISSN: 2227-9059
Open access status: Gold
DOI Link: https://doi.org/10.3390/biomedicines12030674
Publisher: MDPI
Abstract:
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 [beta-Mercapto-beta,beta-cyclopentamethylenepropionyl1, O-Me-Tyr2, Orn8]-Oxytocin) (1 mu M) (**** p < 0.0001) and atosiban (10 M) in both young and older rats (** p < 0.01); in contrast, cligosiban (1 M and 10 mu M) did not inhibit OT-induced contractions in both young and older rats (p >= 0.05). Interestingly, cligosiban (1 mu M and 10 mu M) significantly reduced the frequency of spontaneous contractions within the bladder of both young (*** p < 0.001) and older rats (**** p < 0.0001), while atosiban (10 mu M) only demonstrated this effect in older rats (** p < 0.01). Furthermore, immunohistochemistry (IHC) analysis revealed significant colocalization of nuclear-specific oxytocin receptors (OXTRs) in the contractile (smooth muscle) cells within young (** p < 0.01) and older rats (* p < 0.05), indicating OT may be a key modulator of bladder contractility.
Citation Styles
Harvard Citation style: Badshah, M., Ibrahim, J., Su, N., Whiley, P., Middendorff, R., Whittaker, M., et al. (2024) Age-Dependent Effects of Oxytocin and Oxytocin Receptor Antagonists on Bladder Contractions: Implications for the Treatment of Overactive Bladder Syndrome, Biomedicines, 12(3), Article 674. https://doi.org/10.3390/biomedicines12030674
APA Citation style: Badshah, M., Ibrahim, J., Su, N., Whiley, P., Middendorff, R., Whittaker, M., & Exintaris, B. (2024). Age-Dependent Effects of Oxytocin and Oxytocin Receptor Antagonists on Bladder Contractions: Implications for the Treatment of Overactive Bladder Syndrome. Biomedicines. 12(3), Article 674. https://doi.org/10.3390/biomedicines12030674
Keywords
AGONIST; CONTINENCE SOCIETY; EXTENDED-RELEASE; Lower urinary tract symptoms; overactive bladder; oxytocin; oxytocin receptor antagonist; VASOPRESSIN
