Gallbladder muscle dysfunction in patients with chronic acalculous disease.
OBJECTIVE
The mechanisms responsible for the abnormalities of gallbladder emptying in patients with chronic acalculous gallbladder disease (AGD) have not been elucidated. This study was designed to determine whether a muscle defect could explain this gallbladder dysfunction.


METHODS
Gallbladder contraction induced by a continuous intravenous cholecystokinin octapeptide (CCK-8) infusion was determined by ultrasonography in control subjects, patients with AGD, pigment stones, and cholesterol stones. Muscle cells were obtained by enzymatic digestion. (125)I-CCK-8 binding and [(35)S]guanosine triphosphate gamma S (GTP gamma S) binding studies were performed.


RESULTS
In vivo gallbladder contraction induced by CCK-8 was significantly lower in AGD (29.4%) and cholesterol stones (28.8%) than in pigment stones (59.8%) and normal controls (57.8%; P < 0.01). In vitro muscle cell contraction induced by CCK-8 was also lower in AGD than in pigment stones. It remained impaired in AGD after stimulation with the G-protein activators GTP gamma S and AlF(4) and with the second messenger 1,2-dioctanoyl-sn-glycerol. However, GTP gamma S binding induced by CCK-8 and vasoactive intestinal polypeptide and the binding capacity of CCK receptors were not different between AGD and pigment stones.


CONCLUSIONS
These findings suggest that there is a good correlation between in vivo and in vitro gallbladder response to CCK-8 in patients with AGD. Unlike those found in cholesterol stones, the muscle defects in AGD appear to reside in the contractile apparatus.
Amaral
J
J
Department of Surgery, Rhode Island Hospital and Brown University School of Medicine, Providence, Rhode Island, USA.
Xiao
Z L
ZL
Chen
Q
Q
Yu
P
P
Biancani
P
P
Behar
J
J
D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002769:Cholelithiasis / Q000000981:diagnostic imaging / Q000503:physiopathology; D002784:Cholesterol; D002908:Chronic Disease; D003085:Colic / Q000000981:diagnostic imaging / Q000503:physiopathology; D004075:Diglycerides / Q000494:pharmacology; D005704:Gallbladder / Q000503:physiopathology*; D005705:Gallbladder Diseases / Q000000981:diagnostic imaging / Q000503:physiopathology*; D016473:Gallbladder Emptying / Q000187:drug effects / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D009130:Muscle, Smooth / Q000503:physiopathology; D011949:Receptors, Cholecystokinin / Q000378:metabolism; D012844:Sincalide / Q000008:administration & dosage / Q000378:metabolism; D013462:Sulfur Radioisotopes; D014463:Ultrasonography; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism / Q000494:pharmacology
D004075:Diglycerides; D007457:Iodine Radioisotopes; D011949:Receptors, Cholecystokinin; D013462:Sulfur Radioisotopes; D014660:Vasoactive Intestinal Peptide; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D002784:Cholesterol; D012844:Sincalide