Effect of lead on cholinergic contractile function in the forestomach, ileum and colon of the male Wistar rat
Gastrointestinal symptoms, including colic, are signs of lead poisoning in man, but the mechanism of these effects has not been elucidated. In order to understand the effects of lead on acetylcholine (ACh)-mediated responses, studies were undertaken to determine the isometric contractile response to methacholine, KCl and electric field stimulation in rat forestomach, ileum and colon under conditions of in vitro and in vivo treatment with lead acetate. Rats were dosed with 4% lead acetate in their diet, NIH-07, for 7 weeks, which resulted in renal and hematologic toxicity and blood lead levels of 180-389 ug/dl (1.2 x 10/sup -5/ M). Tissues from in vivo treated rats were exposed to 1.2 x 10/sup -5/ M lead acetate during in vitro contractile studies. E/sub max/ or ED/sub 50/ methacholine was not affected by 1.2 x 10/sup -5/ M lead acetate, administered in vitro to control tissue. In the forestomach, a 10-fold higher concentration of lead (16 x 10/sup -5/ M), administered in vitro, increased baseline tension and inhibition response to methacholine. However, in vivo lead treatment potentiated response to methacholine in the forestomach and increased baseline tension in the presence of physostigmine. The EFS response, attributable to ACh release, was not affected in the forestomach or ileum by 1.2 x 10/sup -5/ M in vitro lead treatment. These data indicate that lead, administered in vivo in concentrations which cause renal and hematologic toxicity, does not impair cholinergic contractile response in gastrointestinal smooth muscle. Instead, the response to methacholine may be potentiated in the forestomach. Possible mechanisms of lead-induced potentiation of baseline or evoked tension include increased levels of non-elicited ACh release, inhibition of acetylcholinesterase or sensitization of muscarinic receptors.
- Research Organization:
- Boston Univ., MA (USA)
- OSTI ID:
- 6989090
- Resource Relation:
- Other Information: Thesis (Ph. D.)
- Country of Publication:
- United States
- Language:
- English
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LEAD COMPOUNDS
BIOLOGICAL EFFECTS
TISSUE DISTRIBUTION
ACETATES
ACETYLCHOLINE
BIOELECTRICITY
BLOOD CHEMISTRY
DIET
ELECTRIC FIELDS
IN VITRO
IN VIVO
KIDNEYS
LARGE INTESTINE
MALES
RATS
SMALL INTESTINE
STOMACH
AMINES
AMMONIUM COMPOUNDS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BODY
CARBOXYLIC ACID SALTS
DIGESTIVE SYSTEM
DISTRIBUTION
DRUGS
ELECTRICITY
ESTERS
GASTROINTESTINAL TRACT
INTESTINES
MAMMALS
NEUROREGULATORS
ORGANIC COMPOUNDS
ORGANS
PARASYMPATHOMIMETICS
QUATERNARY COMPOUNDS
RODENTS
VERTEBRATES
560300* - Chemicals Metabolism & Toxicology