The effect of lead on cholinergic contractile function in the rat forestomach

Previous studies have demonstrated that subchronic exposure to lead in rats slows gastric emptying. Therefore, the isometric contractile response of the forestomach from lead-treated rats was examined in vitro. Male Wistar rats were fed 4% lead acetate in their diet (NIH-07); controls were pair-fed. After 7 weeks, blood lead levels reached 180-389 micrograms/dl. The forestomach was dissected and suspended in buffer which for lead-treated rats contained 1.2 X 10(-5) M lead acetate. Subchronic lead exposure had no effect on the maximum tonic contraction induced by KCl, methacholine or serotonin. However, lead-treated tissue showed enhanced sensitivity to methacholine with a reduction in EC50 to 59.7% of control. This effect was not observed in control tissue exposed to lead (1.2 X 10(-5) M) only in vitro. Higher in vitro concentrations of lead (16 X 10(-5) M) produced an increase in methacholine EC50. Physostigmine-induced increase in tension was also significantly greater in tissue from lead-treated rats. Electric field stimulation, which produced a contraction attributable to postganglionic acetylcholine release, was unaltered in lead-treated tissue. These results indicate that lead intoxication did not impair the contractile apparatus of the forestomach smooth muscle. The lack of net effect on activation of intramural cholinergic neurons, despite the enhanced sensitivity to a cholinergic agonist, may indicate reduction in acetylcholine release in lead-treated tissue.