title: The selective cyclooxygenase-2 inhibitor parecoxib markedly improves the ability of the duodenum to regulate luminal hypertonicity in anaesthetized rats.
abstract: OBJECTIVE
  To examine whether the prevention of post-operative duodenal ileus by treatment with parecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, affects the ability of the duodenum to respond to luminal hypertonicity.
  
  
  METHODS
  The proximal duodenums of anaesthetized rats were perfused with hypertonic NaCl solutions with osmolalities of 400, 500, 600 or 700 mOsm kg(-1) , and the effects on mucosal permeability, motility, transepithelial net fluid flux and effluent osmolality were assessed in the absence (control) and presence of parecoxib.
  
  
  RESULTS
  Parecoxib-treated, but not control animals, exhibited duodenal contractions, which were reduced by the nicotinic receptor antagonists mecamylamine and hexamethonium and by perfusion with 700 mOsm kg(-1) . All animals responded to luminal hypertonicity with induction of net fluid secretion, which peaked at an osmolality of 500 mOsm kg(-1) . The hypertonicity-induced increases in fluid secretion were twofold greater in parecoxib-treated than in control rats and attenuated by nicotinic receptor blockade. The decrease in luminal osmolality correlated with the osmolality of the perfusion solution in both control and parecoxib-treated animals but the osmolality-adjusting capability was markedly better in the latter group. Rats exposed to duodenal luminal distension responded to hypertonicity with a greater fluid secretion and a larger decrease in luminal osmolality than control rats. Perfusion with 700 mOsm kg(-1) increased mucosal permeability in parecoxib-treated animals only, an effect abolished by nicotinic receptor blockade.
  
  
  CONCLUSIONS
  Parecoxib markedly improved the ability of the duodenum to sense and to decrease luminal hypertonicity by a mechanism most probably involving inhibition of COX-2 and stimulation of nicotinic acetylcholine receptors.
authors.affiliation: Division of Physiology, Department of Neuroscience, Biomedical Center, Uppsala University, Uppsala, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Sedin
authors.forename: M
authors.initials: M
authors.lastname: Sjöblom
authors.forename: O
authors.initials: O
authors.lastname: Nylander
mesh_terms: D000818:Animals; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology*; D004386:Duodenum / Q000187:drug effects* / Q000502:physiology*; D007555:Isoxazoles / Q000494:pharmacology*; D008297:Male; D023421:Models, Animal; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009122:Muscle Hypertonia / Q000503:physiopathology*; D009130:Muscle, Smooth / Q000187:drug effects / Q000503:physiopathology; D009994:Osmolar Concentration; D051381:Rats; D011919:Rats, Inbred Strains; D011978:Receptors, Nicotinic / Q000187:drug effects; D012044:Regression Analysis; D012462:Saline Solution, Hypertonic / Q000494:pharmacology; D014474:Unconsciousness / Q000503:physiopathology*
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D007555:Isoxazoles; D011978:Receptors, Nicotinic; D012462:Saline Solution, Hypertonic; C409945:parecoxib