The potential site of disordered gallbladder contractility during the early stage of cholesterol gallstone formation.
OBJECTIVE
Feeding a high cholesterol diet to dogs causes a reduction in gallbladder smooth muscle contractility with a consequent stasis. Gallbladder stasis is an important link between the hepatic secretion of cholesterol saturated bile and the formation of cholesterol gallstones.


METHODS
In this study we tried to localize the probable site of gallbladder smooth muscle dysfunction in a well established animal model of cholesterol gallstone disease. Adult male dogs were fed either a high or low cholesterol diet (control group). Strips of gallbladder smooth muscle for tension development were stimulated with two groups of agonists and dose response curves were plotted for all agonists used.


RESULTS
The forces developed in response to the first group of agonists, the cell membrane-active agonists, e.g. acetylcholine, cholecystokinin, and potassium chloride were decreased in high cholesterol fed dogs with an increased cholesterol saturation of bile when compared to the control group. On the other hand, the contractile response showed non-significant differences between the test and the control group on using the second group of agonists that bypass the intact sarcolemmal membrane and stimulate directly either the contractile mechanism, e.g. barium, or the intracellular signal transduction pathways e.g. aluminum fluoride.


CONCLUSIONS
We conclude that the smooth muscle defect responsible for disordered gallbladder contractility in high cholesterol fed dogs most probably involves the sarcolemmal membrane.
Mansour
A
A
Department of Physiology, Faculty of Medicine, Mansoura University, Egypt.
Dawoud
I
I
Gad-El-Hak
N
N
D000109:Acetylcholine / Q000494:pharmacology; D017607:Aluminum Compounds / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology; D002769:Cholelithiasis / Q000737:chemistry / Q000503:physiopathology*; D002784:Cholesterol; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005459:Fluorides / Q000494:pharmacology; D005704:Gallbladder / Q000187:drug effects / Q000503:physiopathology*; D016473:Gallbladder Emptying; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000502:physiology / Q000648:ultrastructure; D011188:Potassium / Q000494:pharmacology; D012508:Sarcolemma / Q000187:drug effects / Q000502:physiology
D017607:Aluminum Compounds; D002791:Cholesterol, Dietary; D001464:Barium; D002766:Cholecystokinin; D002784:Cholesterol; D000109:Acetylcholine; D005459:Fluorides; D011188:Potassium; C032311:aluminum fluoride