Int Neurourol J.  2016 Sep;20(3):197-202. 10.5213/inj.1632634.317.

Abnormal Sensory Protein Expression and Urothelial Dysfunction in Ketamine-Related Cystitis in Humans

• Tsai YC
• Birder L
• Kuo HC

• KMID: 2365712
• DOI: http://doi.org/10.5213/inj.1632634.317

Abstract

PURPOSE
The aim of this study was to analyze patterns of sensory protein expression and urothelial dysfunction in ketamine-related cystitis (KC) in humans.
METHODS
Biopsies of bladder mucosa were performed in 29 KC patients during cystoscopy. Then specimens were analyzed for tryptase, zonula occludens-1 (ZO-1), E-cadherin, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) with immunofluorescence staining and quantification. In addition, 10 healthy control bladder specimens were analyzed and compared with the KC specimens. Another 16 whole bladder specimens obtained from partial cystectomy were also analyzed for the muscarinic receptors M2 and M3, endothelial nitric oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), β-3 adrenergic receptors (β3-ARs), and the P2X₃ receptor by western blotting. In addition, 3 normal control bladder specimens were analyzed and compared with the KC specimens.
RESULTS
The KC bladder mucosa revealed significantly less expression of ZO-1 and E-cadherin, and greater expression of TUNEL and tryptase activity than the control samples. The expression of M3 and β3-AR in the KC specimens was significantly greater than in the controls. The expression of iNOS, eNOS, M2, and P2X3 was not significantly different between the KC and control specimens.
CONCLUSIONS
The bladder tissue of KC patients revealed significant urothelial dysfunction, which was associated with mast-cell mediated inflammation, increased urothelial cell apoptosis, and increased expression of the M3 and β3-AR.

Keyword

Ketamine; Urothelium

MeSH Terms

Apoptosis
Biopsy
Blotting, Western
Cadherins
Cystectomy
Cystitis*
Cystoscopy
Fluorescent Antibody Technique
Humans*
In Situ Nick-End Labeling
Inflammation
Ketamine
Mucous Membrane
Nitric Oxide Synthase Type II
Nitric Oxide Synthase Type III
Receptor, Muscarinic M2
Receptors, Adrenergic
Tryptases
Urinary Bladder
Urothelium
Cadherins
Ketamine
Nitric Oxide Synthase Type II
Nitric Oxide Synthase Type III
Receptor, Muscarinic M2
Receptors, Adrenergic
Tryptases