TY - JOUR
T1 - Effects of mercuric chloride and methyl mercury on cholinergic neuromuscular transmission in the guinea-pig ileum
AU - Candura, Stefano M.
AU - D'Agostino, Gianluigi
AU - Castoldi, Anna F.
AU - Messori, Eliana
AU - Liuzzi, Maddalena
AU - Manzo, Luigi
AU - Tonini, Marcello
PY - 1997
Y1 - 1997
N2 - 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.
AB - 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.
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M3 - Article
C2 - 9181600
AN - SCOPUS:0030917169
VL - 80
SP - 218
EP - 224
JO - Pharmacology and Toxicology
JF - Pharmacology and Toxicology
SN - 0901-9928
IS - 5
ER -