Stimulation of submucosal glands by nicotine applied locally to the airway mucosa.
Chronic bronchitis is characterized by hypersecretion of mucus and is caused by cigarette smoking. We investigated the effect of nicotine on mucus secretion from tracheal submucosal glands, applying nicotine to the airway mucosa in vitro. We anesthetized 50 ferrets with pentobarbital (66 mg/kg), excised their tracheae and mounted tracheal segments in Ussing chambers. We added 50 microCi Na(2)35SO4 (35S) to the submucosal side and determined nondialyzable 35S in medium collected from the luminal side at 15 min intervals. Nicotine was a powerful stimulant of mucus secretion with threshold effects at 10(-5) M and peak effects at 3 x 10(-4) M. Percentage increases were the same for males and females, but absolute increases in mucus secretion were significantly larger in males than in females. Luminal nicotine was more effective than submucosal nicotine, especially when nicotine bitartrate was used (increase above baseline, 150 +/- 54 vs 22 +/- 12 cpm/15 min, 10(-4) M, n = 4, bitartrate). Effects of luminal nicotine sulfate were larger than those of luminal nicotine bitartrate (303 +/- 88 vs 120 +/- 38 cpm/15 min, P less than 0.05, n = 6, 10(-4) M). Two applications of nicotine 1.5 h apart had similar effects up to 3 x 10(-5) M. At higher concentrations the second response was significantly weaker than the first (tachyphylaxis). Secretory effects of nicotine were prevented completely by atropine and were reduced significantly by hexamethonium.(ABSTRACT TRUNCATED AT 250 WORDS)
Hümmer
B
B
Medizinische Poliklinik, Universität Würzburg.
Purnama
I
I
Hahn
H L
HL
D000287:Administration, Topical; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005289:Ferrets; D009092:Mucous Membrane / Q000187:drug effects; D009093:Mucus / Q000378:metabolism*; D009538:Nicotine / Q000494:pharmacology*; D011950:Receptors, Cholinergic / Q000187:drug effects; D014132:Trachea / Q000187:drug effects*
D011950:Receptors, Cholinergic; D009538:Nicotine