Tetrodotoxin-induced changes in the chemical coding of inferior mesenteric ganglion (IMG) neurons supplying porcine urinary bladder
Article published in Urologia Polska 2008/61/Supl. 1.

authors

Joanna Wojtkiewicz, Agnieszka Bossowska, Artur Zapart, Cezary Skobowiat, Andrzej Borkowski, Piotr Radziszewski, Mariusz Majewski

Katedra Fizjologii Człowieka, Wydział Nauk Medycznych, Uniwersytet Warmińsko-Mazurski w Olsztynie
Klinika Urologii Ogólnej, Onkologicznej i Czynnościowej Warszawskiego Uniwersytetu Medycznego

summary

Introduction.

Tetrodotoxin is a potent neurotoxin, whose mode of action is based on a highly-specific blocking of fast sodium channels in nerve cell membrane what, in turn, abolish the propagation of the action potential along the nerve fiber. Currently, TTX is used in experimental therapies focused on neoplastic or neurogenic pain. However, as of now there is no data concerning the influence of TTX on sympathetic neurons, also on those supplying the urinary bladder.

Objectives.

The present study was aimed at revealing the chemical coding of IMG neurons supplying urinary bladder of the pig (used here as an animal model of the human organ), after intravesical instillation of TTX.

Materials and methods.

Urinary bladder wall was injected with retrograde tracer Fast Blue (FB) in twelve juvenile female pigs and an intravesical instillation of TTX (0.12 μg per animal) was performed three week later in six of them. One week later, IMGs were collected from all animals and were processed for a routine single- and double-immunofluorescence labeling on 10 μm-thick cryostat sections.

Results.

In control animals, the vast majority of FB+ neurons contained tyrosine hydroxylase/ dopamine β-hydroxylase (TH/DβH) and/or neuropeptide Y(NPY-IR (95% and 85% of all retrogradely labeled neurons, respectively). A small number of FB+ cells contained also somatostatin (SOM), vasoactive intestinal polypeptide (VIP), calbidin (CB) and galanin (GAL; 2.2%; 2%; 1.7% and 1.2%, respectively). One week after TTX instillation, a significant decrease (till 7.5%) in the number of FB+ neurons containing neuropeptide Y (NPY) was observed, while the numbers of SOM-, GAL- or CB-IR neurons increased (up to 53%, 14% and 12% of all FB+ neurons, respectively).

Conclusions.

As may be judged from the present study, intravesical instillation of TTX leads to profound changes in the chemical coding of sympathetic neurons supplying the urinary bladder. The observed increase in the number of SOM- or GAL-IR neurons in studied IMGs may suggest that the instillations with this neurotoxin may be used in cases of insufficiency of the sympathetic component of the peripheral nervous system supplying the bladder. However, this assumption needs to be verified in

detail in further studies.