Effects of melatonin on gallbladder neuromuscular function in acute cholecystitis.
Gallbladder stasis is associated to experimental acute cholecystitis. Impaired contractility could be, at least in part, the result of inflammation-induced alterations in the neuromuscular function. This study was designed to determine the changes in gallbladder neurotransmission evoked by acute inflammation and to evaluate the protective and therapeutic effects of melatonin. Experimental acute cholecystitis was induced in guinea pigs by common bile duct ligation for 2 days, and then the neuromuscular function was evaluated using electrical field stimulation (EFS; 5-40 Hz). In a group of animals with the bile duct ligated for 2 days, a deligation of the duct was performed, and after 2 days, the neuromuscular function was studied. The EFS-evoked isometric gallbladder contraction was significantly lower in cholecystitic tissue. In addition, inflammation changed the pharmacological profile of these contractions that were insensitive to tetrodotoxin but sensitive to atropine and omega-conotoxin, indicating that acute cholecystitis affects action potential propagation in the intrinsic nerves. Nitric oxide (NO)-mediated neurotransmission was reduced by inflammation, which also increased the reactivity of sensitive fibers. Melatonin treatment prevented qualitative changes in gallbladder neurotransmission, but it did not improve EFS-induced contractility. The hormone recovered gallbladder neuromuscular function once the biliary obstruction was resolved, even when the treatment was started after the onset of gallbladder inflammation. These findings show for the first time the therapeutic potential of melatonin in the recovery of gallbladder neuromuscular function during acute cholecystitis.
Gomez-Pinilla
Pedro J
PJ
Department of Physiology, Nursing School, Avda Universidad s/n, 10071 Cáceres, Spain.
Camello
Pedro J
PJ
Pozo
María J
MJ
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology* / Q000627:therapeutic use; D041881:Cholecystitis, Acute / Q000188:drug therapy / Q000503:physiopathology*; D004195:Disease Models, Animal; D005704:Gallbladder / Q000187:drug effects* / Q000294:innervation; D006168:Guinea Pigs; D008297:Male; D008550:Melatonin / Q000494:pharmacology* / Q000627:therapeutic use; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000294:innervation; D009469:Neuromuscular Junction / Q000187:drug effects*; D009435:Synaptic Transmission / Q000187:drug effects*
D000975:Antioxidants; D008550:Melatonin