Inhibitory effect of lead acetate on contractility of longitudinal smooth muscle from rat ileum.

The effect of lead acetate on contractility of ileal longitudinal smooth muscle was determined in vitro. Strips, removed from the ileum of male Wistar rats, were suspended in Tris buffer and isometric tension was recorded. Responses to muscarinic receptor activation with methacholine and membrane depolarization with KCl were measured before and after addition of lead acetate to the tissue bath. Lead concentrations of 1 and 3.2 microM had no effect on methacholine (0.45 microM) or KCl (80 mM) induced contractions. However, at concentrations of 10 to 32 microM lead produced a concentration-dependent decline in the response to both these agonists. Both the receptor affinity and intrinsic activity of methacholine were reduced by 160 microM lead. This concentration of lead also inhibited the contractions induced by cumulative addition of calcium chloride (0.18-4.5 mM) to calcium-depleted, KCl-depolarized tissue. This inhibition could be overcome by increased concentrations of calcium. The decreased response to muscarinic receptor activation by methacholine and to membrane depolarization by KCl could result from the impairment of calcium influx or intracellular function.