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 language | English |
|---|---|
| Pages (from-to) | 238-247 |
| Number of pages | 10 |
| Journal | Nishinihon Journal of Urology |
| Volume | 67 |
| Issue number | 5 |
| Publication status | Published - May 2005 |
Fingerprint
Keywords
- ATP
- C-fiber
- Capsaicin
- Isolectin-B4
- Rat
ASJC Scopus subject areas
- Urology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Investigation of the neural mechanisms controlling lower urinary tract using isolectin B4-conjugated saporin, a targeting cytotoxin
AU - Nishiguchi, Jun
AU - Yokoyama, Teruhiko
AU - Sasaki, Katsumi
AU - Kumon, Hiromi
AU - Seki, Satoshi
AU - Chancellor, Michael B.
AU - Yoshimura, Naoki
PY - 2005/5
Y1 - 2005/5
N2 - 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.
AB - 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.
KW - ATP
KW - C-fiber
KW - Capsaicin
KW - Isolectin-B4
KW - Rat
UR - http://www.scopus.com/inward/record.url?scp=20444427611&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=20444427611&partnerID=8YFLogxK
M3 - Article
AN - SCOPUS:20444427611
VL - 67
SP - 238
EP - 247
JO - Nishinihon Journal of Urology
JF - Nishinihon Journal of Urology
SN - 0029-0726
IS - 5
ER -