title: Non-adrenergic, non-cholinergic regulation of stone-diseased and stone-free human gallbladders.
abstract: OBJECTIVE
  The aim of this study was to determine the role of nitric oxide (NO), as the primary neurotransmitter of non-adrenergic, non-cholinergic (NANC) innervation, in stone-diseased and stone-free human gallbladders.
  
  
  METHODS
  Human gallbladder muscle strips were mounted in modified Krebs-Henseleit solution with atropine (1 mM), guanethidine sulfate (5 mM) and aerated with Carbogen. Electric field stimulation (EFS) (70 V, 0.5 ms, 100 pulses) was used to activate NANC nerves. N-omega-nitro-L-arginine (L-NNA, 100 mM) and L-arginine (L-Arg, 120 mM) were used to manipulate the NO-synthase. Gallbladder slices were stained by using the alkaline phosphatase, anti-alkaline phosphatase (APAAP) method for histological examination.
  
  
  RESULTS
  In the control group (basal tone, 8.94 +/- 1.17 mN) caused a frequency-dependent reduction of basal tone (1 Hz = 5.73 +/- 0.81 mN; 3 Hz = 5.18 +/- 0.65 mN; 10 Hz = 4.63 +/- 0.49 mN), inhibition of NO-synthesis with L-NNA increased the tone (7.63 +/- 0.76 mN). Stone-diseased groups were divided into two groups (contractor and subcontractor), according to their ability to contract by CCK. Under the influence of EFS the contractor group (basal tone = 7.79 +/- 0.93 mN) reacted like the control group, but was frequency-independent and, additionally, showed spontaneous phasic contractions. In the sub-contractor group (basal tone 4.13 +/- 0.65 mN) EFS only decreased the frequency of spontaneous phasic contractions. L-NNA caused an increase in tone (5.97 +/- 0.84 mN) and frequency. L-arginine, the substrate for NO-synthase, significantly reversed this effect, indicating the dependence on NO. Histologically, the contractor group showed a wrinkled mucosal membrane and low-grade inflammation. Shallow mucosa, necrosis and high-grade inflammation were found in the sub-contractor group.
  
  
  CONCLUSIONS
  In vitro, NANC relaxation of human gallbladder is NO dependent. The motility of stone-diseased gallbladders is modulated by NO and seems to depend on the degree of scarification.
authors.affiliation: Department of General Surgery, Johann Wolfgang Goethe University, Frankfurt/Main, Germany.
authors.forename: P R
authors.initials: PR
authors.lastname: Sänger
authors.forename: D W
authors.initials: DW
authors.lastname: Sommerfeldt
authors.forename: E W
authors.initials: EW
authors.lastname: Hanisch
mesh_terms: D000328:Adult; D000368:Aged; D002769:Cholelithiasis / Q000473:pathology / Q000503:physiopathology*; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D005704:Gallbladder / Q000187:drug effects / Q000473:pathology / Q000502:physiology* / Q000503:physiopathology*; D005765:Gastrointestinal Agents / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D019335:Nitroarginine / Q000494:pharmacology; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors; D012844:Sincalide / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D005765:Gastrointestinal Agents; D043886:Receptor, Cholecystokinin A; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; D019335:Nitroarginine; D009569:Nitric Oxide; D013779:Tetrodotoxin; D019001:Nitric Oxide Synthase; D012844:Sincalide