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Altered substance P expression in urinary bladder urothelium from cats diagnosed with interstitial cystitis

Amanda Wolf‐Johnston, C. A. Tony Buffington, James R. Roppolo, Changfeng Tai, Anthony Kanai, William C. de Groat, Lori A. Birder

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Abstract

Our studies have revealed that the bladder urothelium exhibits neuron‐like properties and can express a variety of sensor molecules and release chemical mediators. The proximity of the urothelial cells to the nerves suggests that there may be a bidirectional communication between these two cell types. One such chemical mediator, the neurotransmitter Substance P (SP), has been shown to play a role in bladder function, as well as in nociceptive response. Our collaborators have shown that high affinity SP binding sites are upregulated in cats diagnosed with interstitial cystitis (IC), a chronic pelvic painful condition of unknown origin that presents with varying and complex sensory symptoms. The present experiments determined by ELISA if SP levels are altered in urinary bladder mucosa of cats of both sexes with IC. Increased SP levels were detected in the urinary bladder mucosa tissue extracts (1.9‐fold increase) compared to normal unaffected cat urinary bladder mucosa. This evidence lends support to the hypothesis whereby increased SP expression in the urinary bladder mucosa could alter the function of the adjacent afferent/efferent terminals. Thus, treatments which target urothelial release mechanisms or receptors/ion channels in urothelium may be promising for the treatment of a number of painful bladder syndromes. Supported by NIH RO1 DK57284

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What this paper is about

Our studies have revealed that the bladder urothelium exhibits neuron‐like properties and can express a variety of sensor molecules and release chemical mediators. The proximity of the urothelial cells to the nerves suggests that there may be a bidirectional communication between these two cell types. One such chemical mediator, the neurotransmitter Substance P (SP), has been shown to play a role in bladder function, as well as in nociceptive response. Our collaborators have shown that high affinity SP binding sites are upregulated in cats diagnosed with interstitial cystitis (IC), a chronic pelvic painful condition of unknown origin that presents with varying and complex sensory symptoms. The present experiments determined by ELISA if SP levels are altered in urinary bladder mucosa of cats of both sexes with IC. Increased SP levels were detected in the urinary bladder mucosa tissue extracts (1.9‐fold increase) compared to normal unaffected cat urinary bladder mucosa. This evidence lends support to the hypothesis whereby increased SP expression in the urinary bladder mucosa could alter the function of the adjacent afferent/efferent terminals. Thus, treatments which target urothelial release mechanisms or receptors/ion channels in urothelium may be promising for the treatment of a number of painful bladder syndromes. Supported by NIH RO1 DK57284

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Available abstract

Our studies have revealed that the bladder urothelium exhibits neuron‐like properties and can express a variety of sensor molecules and release chemical mediators. The proximity of the urothelial cells to the nerves suggests that there may be a bidirectional communication between these two cell types. One such chemical mediator, the neurotransmitter Substance P (SP), has been shown to play a role in bladder function, as well as in nociceptive response. Our collaborators have shown that high affinity SP binding sites are upregulated in cats diagnosed with interstitial cystitis (IC), a chronic pelvic painful condition of unknown origin that presents with varying and complex sensory symptoms. The present experiments determined by ELISA if SP levels are altered in urinary bladder mucosa of cats of both sexes with IC. Increased SP levels were detected in the urinary bladder mucosa tissue extracts (1.9‐fold increase) compared to normal unaffected cat urinary bladder mucosa. This evidence lends support to the hypothesis whereby increased SP expression in the urinary bladder mucosa could alter the function of the adjacent afferent/efferent terminals. Thus, treatments which target urothelial release mechanisms or receptors/ion channels in urothelium may be promising for the treatment of a number of painful bladder syndromes. Supported by NIH RO1 DK57284

Key concepts: Urothelium, Interstitial cystitis, Urothelial Cell, Urinary bladder, Urinary system, Substance P, Efferent, Neurotransmitter

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