naloxone and Cholecystitis

The increased incidence of gallbladder diseases after gastrectomy is discussed with regard to contractile motility of the gallbladder. Ultrasonographic findings and contraction of the gallbladder in response to egg yolk or caerulein were studied before and after gastrectomy at intervals ranging from 2 weeks to 6 months. Enlargement of the gallbladder with accumulation of biliary sludge and hypomotility were frequently observed within a month of operation for gastric cancer, suggesting that biliary stasis is an important contributing factor in postoperative acute cholecystitis. Within 3 months of operation, contraction had recovered to close to preoperative levels and the incidence of biliary sludge formation gradually decreased. Daily administration of an opiate antagonist, naloxone (0.8 mg), significantly improved gallbladder dyskinesia and decreased the incidence of biliary sludge formation within 1 month of gastrectomy.

Topics: Acute Disease; Ceruletide; Cholecystitis; Egg Yolk; Gallbladder; Gastrectomy; Humans; Middle Aged; Muscle Contraction; Naloxone; Postoperative Complications; Stomach Neoplasms

1. Enkephalin immunoreactive nerve fibres have been demonstrated in the gall bladder of various mammals including man. In various tissues, enkephalins are partly degraded by a membrane metallo-endopeptidase, enkephalinase (EC 3.4.24.11). 2. Using 3H-labelled [D-Ala2,Leu5]enkephalin as a substrate, enkephalinase activity, immunoprecipitated by a monoclonal antibody directed against the rabbit kidney enzyme, was demonstrated in the feline gall bladder. Using the same antibody in 125I-labelled form, the peptidase was immunolocalized by autoradiography, mainly in the epithelium. 3. In experimental cholecystitis, elicited by implantation of human gall-stones into the cat gall bladder, the continuous fluid secretion into the lumen was inhibited by exogenous enkephalins. 4. Acetorphan, an enkephalinase inhibitor, was found to block fluid secretion by the inflamed gall bladder via a naloxone-sensitive mechanism, but not to affect fluid transport in the normal gall bladder. The drug also transiently contracted the gall bladder and increased bile outflow from the liver. 5. It is suggested that acetorphan, by reducing the degradation of endogenous enkephalins in the inflamed gall bladder, decreases fluid secretion by the epithelium and that enkephalinase inhibitors may find clinical applications in acute cholecystitis.

Topics: Animals; Bile; Cats; Cholecystitis; Gallbladder; Mucous Membrane; Naloxone; Neprilysin; Thiorphan

1. Endogenous opioid peptides are found in the enteric nervous system in the gastrointestinal tract. The opioid peptide enkephalin, which has anti-secretory action in the small intestine, is also contained in nerves in the gall-bladder wall. 2. In experimental cholecystitis, there is active fluid secretion by the epithelial cells into the gall-bladder lumen, when the intraluminal hydrostatic pressure is low. This fluid secretion to the lumen was abolished by intravenous administration of enkephalin, an effect that was blocked by naloxone pretreatment. The flux of fluid into the lumen was also abolished when the intraluminal hydrostatic pressure was raised to the level initially observed in the inflamed and obstructed gall bladder. Fluid absorption in the normal gall bladder was unaffected by enkephalin. 3. In experimental cholecystitis, naloxone, used as a non-specific antagonist of opiate action, did not affect the gall-bladder mucosal fluid transport observed at a low intraluminal hydrostatic pressure, but it induced fluid secretion when this pressure was high. 4. It is suggested that a raised intraluminal hydrostatic pressure in experimental cholecystitis, which distends the gall bladder, releases endogenous opioids that inhibit active fluid secretion by the gall-bladder epithelial cells. This response may represent a defence mechanism that could be present also in the gastrointestinal tract. In the obstructed and inflamed gall bladder it may prevent progressive distension, ischaemia and perforation of the wall.

Topics: Animals; Body Fluids; Cats; Cholecystitis; Endorphins; Enkephalins; Gallbladder; Hydrostatic Pressure; Mucous Membrane; Naloxone

In experimental cholecystitis there is a net fluid secretion into the gallbladder lumen and an increased release of prostaglandins. Indomethacin and opiates are known to inhibit this mucosal fluid secretion. Intraluminal or intra-arterial administration of prostaglandin E2 reduces basal gallbladder fluid absorption or induces a net fluid secretion to the lumen and also contracts the normal gallbladder. The use of a continuous perfusion technique in anaesthetized cats in this study shows that the effects of prostaglandin E2 on gallbladder function are blocked by intravenous morphine and loperamide. Naloxone does not affect the gallbladder responses to PGE2 administration. As a mechanism of action it is suggested that opiates inhibit secretory and contractile nerves that are activated by prostaglandins in the gallbladder wall. The findings suggest that the pain relieving effects of opiates in cholecystitis and biliary pain partly are due to blocking of the effects by prostaglandins on gallbladder function.

Topics: Animals; Cats; Cholecystitis; Dinoprostone; Female; Gallbladder; Loperamide; Male; Morphine; Muscle Contraction; Naloxone; Perfusion; Piperidines; Prostaglandins E; Water-Electrolyte Balance