Physiological mechanisms mediating enhanced force generation during development and immune sensitization.
We examined the development of acetylcholinesterase (AChase) activity and tracheal smooth muscle (TSM) contraction elicited by acetylcholine (ACh) in a swine model of maturation and a dog model of allergic bronchospasm. Strips of TSM were tethered isometrically at optimal length and responses were expressed as a percentage of the maximum to KCl-substituted perfusate (% KCl). Maximal contraction (ATmax) to ACh in 2-week-old swine (168 +/- 8% KCl) was greater than in 10-week-old swine (142 +/- 2% KCl; p less than 0.02). The AChase inhibitor, physostigmine, augmented ACh-elicited ATmax in 10-week-old (27% increase; p less than 0.01) but not in 2-week-old swine (2% increase; p is NS) and caused a greater increase in sensitivity to muscarinic activation in 2 versus 10 week-old swine (p less than 0.02), thus demonstrating increased contraction of TSM in 2 versus 10-week-old swine, which results at least in part from reduced AChase activity in immature animals. In another study, TSM from ragweed-sensitized dogs demonstrated augmented efficacy to ACh-elicited contraction (180 +/- 6% KCl) compared with TSM from sham-sensitized, littermate controls (163 +/- 4% KCl; p less than 0.05). In the presence of physostigmine, ATmax was not different between ragweed-sensitized and control TSM.(ABSTRACT TRUNCATED AT 250 WORDS)
Mitchell
R W
RW
Department of Medicine, University of Chicago, IL 60637.
Murphy
T M
TM
Leff
A R
AR
D000109:Acetylcholine / Q000494:pharmacology; D000110:Acetylcholinesterase / Q000378:metabolism; D000818:Animals; D004285:Dogs; D007114:Immunization; D066298:In Vitro Techniques; D007700:Kinetics; D009119:Muscle Contraction / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology*; D010277:Parasympathomimetics / Q000494:pharmacology; D010830:Physostigmine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D013552:Swine; D014132:Trachea / Q000276:immunology / Q000502:physiology
D010277:Parasympathomimetics; D011189:Potassium Chloride; D010830:Physostigmine; D000110:Acetylcholinesterase; D000109:Acetylcholine