Mechanisms of histamine-induced contraction of canine airway smooth muscle.
We studied the effects of atropine (10(-10) to 10(-6) M), tetrodotoxin (TTX) (10(-6) g/ml), and neostigmine (10(-7) M) on the histamine dose-response curve of canine tracheal smooth muscle (TSM) in vitro. Pretreatment with atropine or TTX reduced base-line tension in some TSM samples, whereas neostigmine invariably caused contraction of TSM. All concentrations of atropine reduced the maximum isometric tension produced by histamine (Tmax). With 10(-6), 10(-8), and 10(-10) M atropine, Tmax was 57, 74, and 88%, respectively, of its value in paired control samples. Atropine, 10(-9) to 10(-6) M, increased the concentration of histamine which produced 20% of Tmax, whereas 10(-6) M also increased the concentration required to produce 50% of Tmax. TTX reduced tension produced by low concentrations of histamine but had no effect at higher concentrations. Neostigmine shifted the histamine dose-response curve and caused greater tension for any given histamine concentration; Tmax increased by 30% (P less than 0.05). Our data are consistent with spontaneous release of acetylcholine from cholinergic nerves in the airway tissue and suggest that histamine either accelerates this release or interacts supra-additively with the acetylcholine at the smooth muscle.
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001285:Atropine / Q000494:pharmacology; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000494:pharmacology*; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D009388:Neostigmine / Q000494:pharmacology; D011950:Receptors, Cholinergic / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects
D011950:Receptors, Cholinergic; D009388:Neostigmine; D013779:Tetrodotoxin; D001285:Atropine; D006632:Histamine; D000109:Acetylcholine