[Nonadrenergic noncholinergic regulation of gallstone containing and gallstone free human gallbladders]

This study is to determine the role of nitric oxide (NO), as primary neurotransmitter of the non-adrenergic noncholinergic (NANC) innervation, of stone-diseased and stone-free human gallbladders. Human gallbladder muscle strips were mounted in modified Krebs-Henseleit-solution with atropine (1 microM), guanethidine sulf. (5 microM) and aerated with Carbogen. Electrical field stimulation (EFS, 70V, 0.5 ms, 100 pulses) was used at frequencies of 1, 3, 10 Hz to activate NANC nerves, L-omega-nitro-L-arginine (L-NNA, 100 microM), L-arginine (L-ARG, 120 microM) was used to manipulate the NO-synthase. Gallbladder slices of 3 microns were stained by means of APAAP-method (alkaline phosphatase anti alkaline phosphatase) for histological examination. In the control group (basal tone = 8.94 +/- 1.17 mN) EFS 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). Incubation with L-NNA increased the tone (7.63 +/- 0.76 mN). Contractor group (basal tone = 7.79 +/- 0.93 mN) reacted like the control group but frequency independent and additionally with spontaneous phasic contractions. In the non-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 significantly reversed this effect.

Contractor group showed wrinkled mucosal membrane and mild grade of inflammation. Shallow mucosa, necrosis and high grade of inflammation were found in the non-contractor group.

1. In vitro, NANC-relaxation of human gallbladder is NO dependent. 2. Motility of stone-diseased gallbladders is modulated by NO and seems to depend on the degree of scarrification.