The effect of local injection of botulinum toxin A on the immunoreactivity of nNOS in the rat submandibular gland: an immunohistochemical study.
OBJECTIVE
In our study, we intend to investigate the influence of local injections of botulinum toxin A on the activity of neuronal nitric oxide synthase (nNOS) in submandibular glands of adult rats. Since interest has been focused on the role of nitric oxide (NO) as a possible neuromodulator of secretory regulation processes in the upper aerodigestive tract, it was the aim of the present study to show that the toxin also interferes with the metabolic actions of NO on investigated rat submandibular glands. It is of great clinical interest whether the NO pathway is able to influence salivary gland secretion. Increasing of knowledge in this field maybe helpful to treat sialorrhoea, especially in juvenile otolaryngologic and neurologic patients.


METHODS
We performed immunohistochemical reaction of neuronal nitric oxide synthase (nNOS) in the submandibular gland of female adult Wistar rats, both in native (untreated) glands and after intraglandular injection of botulinum toxin A under general anesthesia. The immunoreactivity of nNOS was investigated on different times after injection.


RESULTS
Other than in the untreated glands, there was a significant decrease of nNOS in the treated organs, which became stronger with extended toxin exposure time. The present study shows explicit data on the effect of botulinum toxin A injection on a higher number of examined submandibular glands and is able to analyze a time course of the effect duration.


CONCLUSIONS
In our study, it was shown that botulinum toxin A had an influence on the immunoreactivity of neuronal nitric oxide synthase (nNOS) in submandibular glands. Therefore, the participation of nitric oxide (NO) in the regulation of secretion from these organs seems to be evident. It might be assumed that the influence of botulinum toxin A on nNOS in the submandibular gland of the rat is able to explain the sometimes longer duration of toxin effect at the neuroglandular junction than at the motor endplate.
Department of Otorhinolaryngology, Head and Neck Surgery, University of Göttingen, Robert-Koch Street 40, D-37075 Göttingen, Germany. mellies@med.uni-goettingen.de
Maik
M
Ellies
Sebastian
S
Schütz
Fabio
F
Quondamatteo
Rainer
R
Laskawi
D000818:Animals; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D007150:Immunohistochemistry / Q000379:methods; D009474:Neurons / Q000187:drug effects / Q000201:enzymology; D009498:Neurotoxins / Q000008:administration & dosage / Q000494:pharmacology*; D009569:Nitric Oxide / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D051381:Rats; D017208:Rats, Wistar; D012798:Sialorrhea / Q000188:drug therapy; D013363:Submandibular Gland / Q000187:drug effects* / Q000201:enzymology
D009498:Neurotoxins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D019274:Botulinum Toxins, Type A