Bladder surface glycosaminoglycans is a human epithelial permeability barrier

Area of Science:

• Urology
• Biochemistry
• Epithelial Biology

Background:

• The bladder's transitional epithelium is traditionally considered impermeable.
• The role of surface glycosaminoglycans (GAG) in bladder permeability is not fully understood.
• Identifying the primary barrier to small molecule transport is crucial for understanding bladder function.

Purpose of the Study:

• To investigate the role of bladder surface glycosaminoglycans (GAG) as a permeability barrier.
• To determine if GAG prevent small molecules like urea from crossing the bladder epithelium.
• To assess the impact of GAG disruption and restoration on urea permeability in human volunteers.

Main Methods:

• Urea permeability studies were conducted in 27 normal volunteers.
• Protamine sulfate was instilled to disrupt surface GAG, followed by a second urea study.
• Heparin was instilled to assess its effect on GAG and urea permeability.

Main Results:

• Baseline urea loss from the bladder lumen was 5.1%.
• Following protamine sulfate treatment, urea loss significantly increased to 22% (p < 0.02).
• Subsequent heparin treatment reduced urea loss to 9%, reversing the effect of protamine sulfate.
• Protamine sulfate caused urinary urgency and discomfort, which were alleviated by heparin.

Conclusions:

• Bladder surface glycosaminoglycans (GAG) function as a significant physical barrier to small molecule permeability.
• These GAG prevent molecules like urea from reaching underlying tight junctions and cell membranes.
• Modulating GAG integrity offers a potential avenue for managing bladder permeability.