Cannabinoid receptor expression in the bladder is altered in detrusor overactivity

Bakali, Evangelia; McDonald, John; Elliott, Ruth A.; Lambert, David G.; Tincello, Douglas G.

doi:10.1007/s00192-015-2802-x

Cited by 18 publications

(23 citation statements)

References 33 publications

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“…Thus it can be postulated that the cannabinoid receptors may affect both bladder motor and sensory functions. Previous studies have shown that activation of CB1/CB2 in human bladder attenuated the electrically evoked contraction of detrusor strips and the receptor expression is reduced in the detrusor of patients with detrusor overactivity . Taken together, these findings have demonstrated the potential importance of the cannabinoid receptors in the human bladder physiology and pathophysiology.…”

Section: Discussionmentioning

confidence: 58%

“…Previous studies have shown that activation of CB1/CB2 in human bladder attenuated the electrically evoked contraction of detrusor strips and the receptor expression is reduced in the detrusor of patients with detrusor overactivity. 18 Taken together, these findings have demonstrated the potential importance of the cannabinoid receptors in the human bladder physiology and pathophysiology. As a result, these receptors have been viewed as a promising future direction in the pharmacotherapy of LUTS.…”

Section: Discussionmentioning

confidence: 79%

“…On the other hand, prior studies in the rat and human bladder showed that the CB1 receptor exerted both pre‐ and post‐synaptic inhibitory effects on bladder contraction, whereas CB2 acted only post‐synaptically . Immunofluorescence study in the human bladder showed co‐localization of cannabinoid receptors with cholinergic nerves which may suggest possible influence on neurotransmitter release . Thus, the exact distribution and function of the cannabinoid receptors in the bladder would require further clarification.…”

Section: Discussionmentioning

confidence: 95%

“…22 Immunofluorescence study in the human bladder showed co-localization of cannabinoid receptors with cholinergic nerves which may suggest possible influence on neurotransmitter release. 18 Thus, the exact distribution and function of the cannabinoid receptors in the bladder would require further clarification.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, cannabinoid receptor stimulation could modulate bladder afferent activity and suppress the chemically‐evoked release of calcitonin gene‐related peptide (CGRP) from the bladder urothelium . More recently, it has been shown that bladder cannabinoid receptor expression is reduced in patients with detrusor overactivity (DO) . These findings suggest that the cannabinoid receptors can serve as a future target for drugs acting on lower urinary tract symptoms (LUTS) including overactive bladder (OAB) and chronic bladder pain syndrome.…”

Section: Introductionmentioning

confidence: 99%

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Metabolic Syndrome Induced Bladder Cannabinoid Receptor Changes in the Fructose‐Fed Rats

Chen

Tong

2017

LUTS

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Section: Discussionmentioning

confidence: 58%

Section: Discussionmentioning

confidence: 79%

Section: Discussionmentioning

confidence: 95%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Metabolic Syndrome Induced Bladder Cannabinoid Receptor Changes in the Fructose‐Fed Rats

Chen

Tong

2017

LUTS

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Lifelong LUTS: Understanding the bladder's role and implications across transition phases, a comprehensive review

Kheir,

Verbakel,

Wyndaele

et al. 2024

Neurourology and Urodynamics

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IntroductionLower urinary tract symptoms (LUTSs) are a diverse array of urinary and pelvic dysfunctions that can emerge from childhood, extend through adulthood, and persist into older age. This narrative review aims to provide a comprehensive perspective on the continuum of LUTS and shed light on the underlying mechanisms and clinical implications that span across the lower urinary tract.MethodsA panel of five experts from Belgium, the Netherlands, India, Denmark, and the United States participated in an intensive research to explore and pinpoint existing insights into the lifelong concept of LUTS, particularly at the pelvic level. The experts reviewed the existing literature and held a webinar to discuss their findings.ResultsChildhood LUTS can persist, resolve, or progress into bladder underactivity, dysfunctional voiding, or pain syndromes. The Lifelong character can be explained by pelvic organ cross‐talk facilitated through complex neurological and nonneurological interactions. At the molecular level, the role of vasopressin receptors in the bladder's modulation and their potential relevance to therapeutic strategies for LUTS are explored. Frailty emerges as a parallel concept to lifelong LUTS, with a complex and synergistic relationship. Frailty, not solely an age‐related condition, accentuates LUTS severity with insufficient evidence regarding the effectiveness and safety profile of the available therapeutic modalities.ConclusionUnderstanding lifelong LUTSs offers insights into genetic, anatomical, neurological, and molecular mechanisms. Further research could identify predictive biomarkers, elucidate the role of clinically translatable elements in pelvic cross‐talk, and uncover molecular signatures for personalized management.

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Improvement of lower urinary tract dysfunction by a monoacylglycerol lipase inhibitor in mice with spinal cord injury

Cho,

Hashimoto,

Karnup

et al. 2024

Neurourology and Urodynamics

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AimsActivation of the endocannabinoid system by monoacylglycerol lipase (MAGL) blockade may affect the lower urinary tract function. We investigated the effect of an MAGL inhibitor, MJN110, on neurogenic lower urinary tract dysfunction (LUTD) in the mouse model of spinal cord injury (SCI).MethodsFemale C57BL/6 mice that underwent spinal cord transection at T8–10 level were divided into three groups consisting of (1) vehicle‐treated SCI mice, (2) 5 mg/kg, or (3) 10 mg/kg of MJN110‐treated SCI mice. MJN110 and vehicle were administered intraperitoneally for 7 days from 4 weeks after spinal cord transection. We then conducted awake cystometrograms and compared urodynamic parameters between three groups. The expression of cannabinoid (CB) receptors, TRP receptors, and inflammatory cytokines in L6‐S1 dorsal root ganglia (DRG) or the bladder mucosa were evaluated and compared among three groups. Changes in the level of serum 2‐arachidonoylglycerol (2‐AG) and bladder MAGL were also evaluated.ResultsIn the cystometrogram, detrusor overactivity (DO) parameters, such as the number of nonvoiding contraction (NVC), a ratio of time to the 1st NVC to intercontraction interval (ICI), and NVC integrals were improved by MJN110 treatment, and some effects were dose dependent. Although MJN110 did not improve voiding efficiency, it decreased bladder capacity, ICI, and residual urine volume compared to vehicle injection. MJN110 treatment groups had lower CB2, TRPV1, TRPA1, and inflammatory cytokines mRNA levels in DRG and bladder mucosa. Serum 2‐AG was increased, and bladder MAGL was decreased after MAGL inhibitor treatment.ConclusionsMAGL inhibition improved LUTD including attenuation of DO after SCI. Thus, MAGL can be a therapeutic target for neurogenic LUTD after SCI.

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Cannabinoid receptor expression in the bladder is altered in detrusor overactivity

Cited by 18 publications

References 33 publications

Metabolic Syndrome Induced Bladder Cannabinoid Receptor Changes in the Fructose‐Fed Rats

Metabolic Syndrome Induced Bladder Cannabinoid Receptor Changes in the Fructose‐Fed Rats

Lifelong LUTS: Understanding the bladder's role and implications across transition phases, a comprehensive review

Improvement of lower urinary tract dysfunction by a monoacylglycerol lipase inhibitor in mice with spinal cord injury

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