Investigation of the neural mechanisms controlling lower urinary tract using isolectin B4-conjugated saporin, a targeting cytotoxin

Jun Nishiguchi, Teruhiko Yokoyama, Katsumi Sasaki, Hiromi Kumon, Satoshi Seki, Michael B. Chancellor, Naoki Yoshimura

Research output: Contribution to journalArticle

Abstract

In order to clarify the functional role of the IB4-binding afferent pathway in the micturition reflex, we investigated the effects on bladder activity of intrathecal application of the isolectin B4 (IB4)-saporin conjugate, a targeting cytotoxin that destroys neurons binding IB4. In rats, IB4-saporin (2.5 μM) or vehicle was administered through an intrathecal catheter implanted at the level of the L6-S1 spinal cord. Three weeks after IB4-saporin administration, cystometry in conscious animals revealed a reduction in bladder overactive responses induced by intravesical capsaicin or ATP infusion without affecting normal voiding function. In histochemical studies, double staining for IB4 and saporin was detected in L6 DRG neurons 2 days after the treatment. Three weeks after the treatment, the area in lamina II of the L6 spinal cord stained with IB4 was significantly reduced compared with the area stained in control rats. Staining in the L1 spinal cord was not affected. The percentage of neurons in the L6 DRG intensely labeled with IB4 was also reduced in IB4-saporin-treated rats. These results indicate that intrathecal treatment with the IB4-saporin conjugate at the level of the L6-S1 spinal cord, which reduces IB4 afferent nerve terminal staining in lamina II of the L6 spinal cord as well as the number of IB4-binding neurons in L6 DRG, suppressed bladder overactivity induced by bladder irritation without affecting normal micturition. Thus targeting IB4-binding, non-peptidergic afferent pathways sensitive to capsaicin and ATP may be an effective treatment for overactivity and/ or pain responses in the bladder.

Original languageEnglish
Pages (from-to)238-247
Number of pages10
JournalNishinihon Journal of Urology
Volume67
Issue number5
Publication statusPublished - May 2005

Fingerprint

Cytotoxins
Urinary Tract
Lectins
Spinal Cord
Diagnosis-Related Groups
Urinary Bladder
Substantia Gelatinosa
Afferent Pathways
Neurons
Urination
Capsaicin
Staining and Labeling
saporin
Adenosine Triphosphate
Overactive Urinary Bladder
Therapeutics
Reflex
Catheters

Keywords

  • ATP
  • C-fiber
  • Capsaicin
  • Isolectin-B4
  • Rat

ASJC Scopus subject areas

  • Urology

Cite this

Nishiguchi, J., Yokoyama, T., Sasaki, K., Kumon, H., Seki, S., Chancellor, M. B., & Yoshimura, N. (2005). Investigation of the neural mechanisms controlling lower urinary tract using isolectin B4-conjugated saporin, a targeting cytotoxin. Nishinihon Journal of Urology, 67(5), 238-247.

Investigation of the neural mechanisms controlling lower urinary tract using isolectin B4-conjugated saporin, a targeting cytotoxin. / Nishiguchi, Jun; Yokoyama, Teruhiko; Sasaki, Katsumi; Kumon, Hiromi; Seki, Satoshi; Chancellor, Michael B.; Yoshimura, Naoki.

In: Nishinihon Journal of Urology, Vol. 67, No. 5, 05.2005, p. 238-247.

Research output: Contribution to journalArticle

Nishiguchi, J, Yokoyama, T, Sasaki, K, Kumon, H, Seki, S, Chancellor, MB & Yoshimura, N 2005, 'Investigation of the neural mechanisms controlling lower urinary tract using isolectin B4-conjugated saporin, a targeting cytotoxin', Nishinihon Journal of Urology, vol. 67, no. 5, pp. 238-247.
Nishiguchi, Jun ; Yokoyama, Teruhiko ; Sasaki, Katsumi ; Kumon, Hiromi ; Seki, Satoshi ; Chancellor, Michael B. ; Yoshimura, Naoki. / Investigation of the neural mechanisms controlling lower urinary tract using isolectin B4-conjugated saporin, a targeting cytotoxin. In: Nishinihon Journal of Urology. 2005 ; Vol. 67, No. 5. pp. 238-247.
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