Inhibitory effect of botulinum toxin type A on the NANC system in rat respiratory models of neurogenic inflammation.
This study investigated whether botulinum toxin type A (BTX-A) inhibits respiratory neurogenic inflammation in the non-adrenergic, non-cholinergic (NANC) transmitter system in rats. Neurogenic inflammation models were induced in Sprague Dawley (SD) rats through bilateral cerebral artery occlusion (BCAO) for different times (0, 30 and 60 min) or by stimulation with capsaicin at different doses (5 or 15 g/kg). Pre-Bötzinger Complex-Spikes and the expression of substance P, synaptosomal-associated protein-25 (SNAP-25), and reactive oxygen species (ROS) were detected with or without pretreatment of rats with BTX-A (15 or 30 U/kg). BCAO reduced pre-Bot C spike activity (spike/s) and increased the breath rate (breaths/s) in an unstable pattern in comparison to controls, while pretreatment with BTX-A slightly reduced this phenomenon. Pretreatment with BTX-A inhibited BCAO- or capsaicin-induced increases in expression of SNAP-25, substance P, and ROS in a dose-dependent manner in brainstem and lung tissue. BTX-A exerts a suppressive effect on neurogenic inflammation via non-adrenergic, non-cholinergic transmitters. These results add to the body of evidence elucidating the non-cholinergic effects of BTX-A in the context of neurogenic inflammation.
Department of Life Science, National Taiwan Normal University, Taipei, Taiwan, ROC.
Chiang-Ting
CT
Chien
Hsin-Min
HM
Lee
Chia-Ching Josh
CC
Wu
Ping-Chia
PC
Li
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000150:complications; D019274:Botulinum Toxins, Type A / Q000494:pharmacology* / Q000627:therapeutic use; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D002211:Capsaicin / Q000494:pharmacology; D004195:Disease Models, Animal; D008168:Lung / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D020078:Neurogenic Inflammation / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D011014:Pneumonia / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013373:Substance P / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25 / Q000378:metabolism
D018377:Neurotransmitter Agents; D017382:Reactive Oxygen Species; D050825:Synaptosomal-Associated Protein 25; D013373:Substance P; D019274:Botulinum Toxins, Type A; D002211:Capsaicin