Sha, L.

AbstractBackgroundOtilonium bromide (OB) is used as a spasmolytic drug in the treatment of the functional bowel disorder irritable bowel syndrome. Although its acute effects on colonic relaxation are well‐characterized, little is known about the effects of chronic administration ofOBon enteric neurons, neuromuscular transmission, and interstitial cells of Cajal (ICC), key regulators of the gut function.MethodsAdult Sprague–Dawley rats were treated withOBin drinking water at a dose of 2 mg/kg for 30 days. The colons ofOB‐treated and age‐matched control rats were studied by confocal immunohistochemistry to detect immunoreactivity (IR) in myenteric plexus neurons for nitrergic and tachykininergic markers, and also by microelectrode electrophysiology.Key ResultsUsing immunohistochemistry, chronicOBadministration did not change total neuron number, assessed by anti‐HuIR, but resulted in a significant increase inNK1 receptor positive neurons, a decrease in neuronal nitric oxide synthase expressing neurons, and a reduction in volume of substance P in nerve fibers in the myenteric plexus. ChronicOBadministration potentiated inhibitory and excitatory junction potentials evoked by repetitive electrical field stimulation. The various types of colonicICC, detected by KitIR, were not altered nor were slow waves or smooth muscle membrane potential.Conclusions & InferencesChronic treatment withOBcaused significant changes in the nitrergic and tachykinergic components of the myenteric plexus and in both inhibitory and excitatory neurotransmission in the rat colon.