Vagal control of mucus glycoconjugate secretion into the feline trachea

1. We examined the effects of frequencies and patterns of electrical stimulation of the peripheral cut ends of the vagus nerves on the release of mucus glycoconjugates into feline trachea in vivo. Mucus glycoconjugates, radiolabelled biosynthetically with [35S]sulphate and [3H]glucose, were washed from a tracheal segment in situ, and dialysed before being counted and assayed chemically by the periodic acid-Schiff (PAS) method. 2. Vagal stimulation with regular pulses (10 V, 2 ms duration) at 1, 2.25, 4.5, 9 and 18 Hz produced frequency-dependent increases in the output of mucus glycoconjugates. 3. The muscarinic agonist pilocarpine (0.1-10 microM), given intrasegmentally, produced dose-dependent increases in the output of mucus glycoconjugates. 4. Pretreatment with atropine, phentolamine and propranolol reduced but did not abolish the effects of vagal stimulation. Vagus nerve stimulation still caused frequency-dependent increases in the output of mucus glycoconjugates. 5. High frequency stimulations at 22.5 and 47.5 Hz given intermittently (1 s burst then 4 s rest), whether in the absence or presence of cholinergic and adrenergic blockade, produced similar secretory responses as the same number of pulses delivered in regular trains at 4.5 and 9.5 Hz. This suggests that neither cholinergic nor non-adrenergic, non-cholinergic (NANC) nerve mechanisms in this system are potentiated by high frequency, intermittent burst stimulation. 6. In the absence of atropine, regular vagal stimulation had a greater effect on heart rate than did the same number of pulses delivered in bursts. 7. High molecular weight glycoconjugates from secretions were taken from the void volume of a Sepharose CL-2B gel filtration column and separated further by density-gradient centrifugation. Macromolecular components were observed at two densities, a typical mucin at 1.52 g ml-1, and a high density atypical component at 1.63 g ml-1. In secretions collected during vagal stimulation, either in the absence or presence of cholinergic and adrenergic blockade, the ratio of low density to high density macromolecules was higher than in unstimulated secretions. This can be explained if both cholinergic and NANC nervous vagal mechanisms stimulate the output of typical (density = 1.52 g ml-1) mucins into the feline trachea.