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 0.33 microM slightly enhanced the amplitude of twitch contractions in approximately 50% preparations. This effect was probably due to facilitation of acetylcholine (ACh) release since 0.1 and 1 microM 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 microM; MeHg IC50 = 45.1 +/- 5.5 microM), as well as contractions to exogenous ACh (0.1 microM) 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 tone 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 Ca(2+)-dependent mechanisms underlying smooth muscle contractility are targets for mercury toxicity in the intestine.
Candura
S M
SM
Department of Internal Medicine and Therapeutics, University of Pavia, Italy.
D'Agostino
G
G
Castoldi
A F
AF
Messori
E
E
Liuzzi
M
M
Manzo
L
L
Tonini
M
M
D000109:Acetylcholine / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D002799:Cholinergic Fibers / Q000187:drug effects* / Q000502:physiology*; D004202:Disinfectants / Q000633:toxicity*; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D007082:Ileum / Q000294:innervation*; D008297:Male; D008627:Mercuric Chloride / Q000633:toxicity*; D008767:Methylmercury Compounds / Q000633:toxicity*; D009119:Muscle Contraction / Q000187:drug effects; D009197:Myenteric Plexus / Q000502:physiology; D009469:Neuromuscular Junction / Q000187:drug effects / Q000502:physiology; D013268:Stimulation, Chemical; D009435:Synaptic Transmission / Q000187:drug effects*; D014316:Tritium
D004202:Disinfectants; D008767:Methylmercury Compounds; D014316:Tritium; D008627:Mercuric Chloride; D000109:Acetylcholine