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) wer e examined on basal mechanical activity and electrically-induced neuro genic cholinergic contractions (twitch contractions) in longitudinal m uscle-myenteric plexus strips from guinea-pig distal ileum. Both compo unds at 0.3-3 mu M slightly enhanced the amplitude of twitch contracti ons in similar to 50% preparations. This effect was probably due to fa cilitation of acetylcholine (ACh) release since 0.1 and 1 mu M mercuri als increased electrically-evoked tritium outflow from [H-3]choline pr eloaded muscle layer with attached myenteric plexus. Conversely, highe r mercury concentrations inhibited twitch contractions (HgCl2 IC50=21. 3+/-6.4 mu M; MeHg IC50=45.1+/-5.5 mu M), as well as contractions to e xogenous ACh (0.1 mu M) in resting preparations, and concomitantly inc reased the basal tone. The former effects possibly reflected an antimu scarinic activity of mercury, while the latter was related to alterati ons of calcium homeostasis in the effector cells. Indeed, the effect o f HgCl2 on basal tone was antagonized by the Ca2+ entry blocker nifedi pine (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 mechan isms underlying smooth muscle contractility are targets for mercury to xicity in the intestine.