Topography of the vanilloid receptor in the human bladder: more than just the nerve fibers.
OBJECTIVE
We determined the presence and distribution of vanilloid receptor-1 in the human bladder and confirmed or rejected previous findings of other groups that used indirect methods or vanilloid receptor-1 antibodies made by immunizing experimental animals. Also, we tested the reproducibility of results using commercially available antibodies against the N-terminus and C-terminus of the vanilloid receptor.


METHODS
A total of 11 normal bladder tissue samples were obtained from cystectomy specimens and fresh frozen processed. Specimens were studied by immunohistochemistry and confocal laser microscopy using 3 vanilloid receptor-1 antibodies. Immunohistochemical co-localization studies for neurofilament, neuronal nitric oxide synthase and nerve growth factor were performed.


RESULTS
Our results confirm the presence of vanilloid receptor-1 on nonmyelinated and myelinated nerve fibers. There was vanilloid receptor-1 immunoreactivity on smooth muscle cells but different sensitivities for the antibodies. There was immunoreactivity on interstitial cells located in the suburothelium and intermuscular septa of the muscularis. There was co-localization of neuronal nitric oxide synthase with interstitial cells but not with neurofilament. No co-localization was found for nerve growth factor and vanilloid receptor-1.


CONCLUSIONS
Vanilloid receptor-1 is located on small unmyelinated and myelinated nerve fibers. In addition, vanilloid receptor-1 is also present on interstitial cells in the suburothelium. There is smooth muscle cell immunoreactivity but a difference in antibodies raised against the C-terminus and N-terminus. These data suggest that the current hypothesis about the mechanism of action of vanilloids is through blocking the afferent reflex arc must be revised and the function of interstitial cells deserves further attention.
Ost
Dieter
D
Department of Urology, University Hospital Gasthuisberg, Leuven, Belgium.
Roskams
Tania
T
Van Der Aa
Frank
F
De Ridder
Dirk
D
D006801:Humans; D007091:Image Processing, Computer-Assisted; D021621:Imaging, Three-Dimensional; D018613:Microscopy, Confocal; D008856:Microscopy, Fluorescence; D009412:Nerve Fibers / Q000000981:diagnostic imaging*; D009413:Nerve Fibers, Myelinated / Q000000981:diagnostic imaging; D020932:Nerve Growth Factor / Q000032:analysis; D016900:Neurofilament Proteins / Q000032:analysis; D019001:Nitric Oxide Synthase / Q000032:analysis; D052248:Nitric Oxide Synthase Type I; D011955:Receptors, Drug / Q000648:ultrastructure*; D015203:Reproducibility of Results; D050916:TRPV Cation Channels; D014463:Ultrasonography; D001743:Urinary Bladder / Q000033:anatomy & histology / Q000294:innervation*
D016900:Neurofilament Proteins; D011955:Receptors, Drug; D050916:TRPV Cation Channels; C494484:TRPV1 receptor; D020932:Nerve Growth Factor; C496320:NOS1 protein, human; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I