P. Sanger et al., NONADRENERGIC NONCHOLINERGIC REGULATION O F STONE-DISEASED AND STONE-FREE HUMAN GALLBLADDERS, Zentralblatt fur Chirurgie, 122(5), 1997, pp. 418-424
This study is to determine the role of nitric oxide (NO), as primary n
eurotransmitter of the non-adrenergic noncholinergic (NANC) innervatio
n, of stone-diseased and stone-free human gallbladders. Human gallblad
der muscle strips were mounted in modified Krebs-Henseleit-solution wi
th atropine (1 mu M), guanethidine sulf. (5 mu M) and aerated with Car
bogen. 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-n
itro-L-arginine (L-NNA, 100 mu M), L-arginine (L-ARG, 120 mu M) was us
ed to manipulate the NO-synthase. Gallbladder slices of 3 mu m were st
ained by means of APAAP-method (alkaline phosphatase anti alkaline pho
sphatase) for histological examination. In the control group (basal to
ne = 8.94+/-1.17 mN) EFS caused a frequency dependent reduction of bas
al tone (1 Hz = 5.73 +/- 0.81 mN; 3 Hz = 5.18 +/- 0.65 mN; 10 Hz = 4.6
3+/-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 contr
ol group but frequency independent and additionally with spontaneous p
hasic contractions. In the non-contractor group (basal tone 4.13+/-0.6
5 mN) EFS only decreased the frequency of spontaneous phasic contracti
ons. L-NNA caused an increase in tone (5.97 +/- 0.84 mN) and frequency
; L-Arginine significantly reversed this effect. Histology: Contractor
group showed wrinkled mucosal membrane and mild grade of inflammation
. Shallow mucosa, necrosis and high grade of inflammation were found i
n the non-contractor group. Conclusions: 1. In vitro, NANC-relaxation
of human gallbladder is NO dependent. 2. Motility of stone-diseased ga
llbladders is modulated by NO and seems to depend on the degree of sca
rrification.