Effects of mercuric chloride and methyl mercury on cholinergic neuromuscular transmission in the guinea-pig ileum

The effects of mercuric chloride (HgCl₂) and methyl mercury (MeHg) were examined on basal mechanical activity and electrically-induced neurogenic cholinergic contractions (twitch contractions) in longitudinal muscle-myenteric plexus strips from guinea-pig distal ileum. Both compounds at 0.3-3 μM slightly enhanced the amplitude of twitch contractions in ~ 50% preparations. This effect was probably due to facilitation of acetylcholine (ACh) release since 0.1 and 1 μM mercurials increased electrically-evoked tritium outflow from [³H]choline preloaded muscle layer with attached myenteric plexus. Conversely, higher mercury concentrations inhibited twitch contractions (HgCl₂ IC₅₀ = 21.3 ± 6.4 μM; MeHg IC₅₀ = 45.1 ± 5.5 μM), as well as contractions to exogenous ACh (0.1 μM) in resting preparations, and concomitantly increased the basal tone. The former effects possibly reflected an antimuscarinic activity of mercury, while the latter was related to alterations of calcium homeostasis in the effector cells. Indeed, the effect of HgCl₂ on basal lone was antagonized by the Ca²⁺ entry blocker nifedipine (3, 10, 30 nM), indicating Hg-induced facilitation of Ca²⁺ influx through voltage-dependent channels. On the whole, our results suggest that cholinergic neuromuscular transmission and Ca²⁺-dependent mechanisms underlying smooth muscle contractility are targets for mercury toxicity in the intestine.