Badshah Masroor, Ibrahim Jibriil, Su Nguok, Whiley Penny, Middendorff Ralf, Whittaker Michael, Exintaris Betty
Hudson Institute of Medical Research, Monash University, Clayton, VIC 3168, Australia.
Monash Institute of Pharmaceutical Sciences, Parkville, VIC 3052, Australia.
Biomedicines. 2024 Mar 18;12(3):674. doi: 10.3390/biomedicines12030674.
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) (**** < 0.0001) and atosiban (10 µM) in both young and older rats (** < 0.01); in contrast, cligosiban (1 µM and 10 µM) did not inhibit OT-induced contractions in both young and older rats ( ≥ 0.05). Interestingly, cligosiban (1 µM and 10 µM) significantly reduced the frequency of spontaneous contractions within the bladder of both young (*** < 0.001) and older rats (**** < 0.0001), while atosiban (10 µM) only demonstrated this effect in older rats (** < 0.01). Furthermore, immunohistochemistry (IHC) analysis revealed significant colocalization of nuclear-specific oxytocin receptors (OXTRs) in the contractile (smooth muscle) cells within young (** < 0.01) and older rats (* < 0.05), indicating OT may be a key modulator of bladder contractility.
膀胱过度活动症（OAB）是一种与年龄相关的疾病，其特征是膀胱收缩不稳定，导致下尿路症状（LUTS）紊乱，从而对个人生活质量产生深远影响。LUTS的发展可能与膀胱逼尿肌中催产素受体（OXTRs）的过度表达有关，导致基线肌源性张力增加。因此，有人提出假设，使用催产素拮抗剂靶向膀胱内的OXTRs可能会减弱膀胱内的肌源性张力，从而为治疗OAB提供一条新的治疗途径。对来自年轻大鼠（7-8周和10-12周）和老年大鼠（4-5个月和7-9个月）的膀胱组织进行了器官浴收缩性和免疫组织化学技术研究。器官浴研究表明，催产素（OT）显著增加膀胱收缩，在年轻和老年大鼠中，[β-巯基-β，β-环五亚甲基丙酰基1，O-甲基-Tyr2，鸟氨酸8]-催产素（1µM）（<0.0001）和阿托西班（10µM）均能显著减弱这种收缩（<0.01）；相比之下，西曲班（1µM和10µM）在年轻和老年大鼠中均未抑制OT诱导的收缩（≥0.05）。有趣的是，西曲班（1µM和10µM）显著降低了年轻（<0.001）和老年大鼠（<0.0001）膀胱内的自发收缩频率，而阿托西班（10µM）仅在老年大鼠中显示出这种效果（<0.01）。此外，免疫组织化学（IHC）分析显示，在年轻（<0.01）和老年大鼠（<0.05）的收缩性（平滑肌）细胞中，核特异性催产素受体（OXTRs）有显著共定位，表明OT可能是膀胱收缩性的关键调节因子。
