Converting gallbladder absorption to secretion: the role of intracellular calcium.
BACKGROUND
Experimental cholelithiasis is associated with elevated biliary calcium concentration and altered gallbladder absorption. Recent studies showed that extracellular calcium ([Ca2+]ec) plays a role in regulating gallbladder ion transport. The extent to which intracellular calcium ([Ca2+]ic) mediates the changes in gallbladder ion transport is not clear. We hypothesize that [Ca2+]ic is an important regulator of gallbladder ion transport.


METHODS
Prairie dog gallbladders were mounted in Ussing chambers, standard electrophysiologic parameters were recorded, and unidirectional Na+, Cl- and H2O fluxes were measured before and after mucosal exposure of 10-5 mol/L calcium ionophore A23187 was performed.


RESULTS
A23187 caused an increase in transepithelial short-circuit current and potential difference and a decrease in transepithelial resistance. A23187 inhibited mucosa to serosa Cl- flux and stimulated serosa to mucosa Na+ flux, resulting in increased net Cl- secretion and decreased net Na+ absorption. A23187 converted H2O from absorption to secretion. Transepithelial short-circuit current effect of A23187 was delayed by indomethacin pretreatment and was completely blunted by low bathing Ca2+.


CONCLUSIONS
This is the first demonstration that increased [Ca2+]ic converts the gallbladder from its normal absorptive state to a secretory one. Furthermore [Ca2+]ic appears to regulate ion transport through mechanisms that are partially prostaglandin-dependent. Studies are necessitated to define possible links between gallbladder secretion of Cl- and H2O and mucus hypersecretion, a well-described phenomenon associated with cholesterol gallstone formation.
Moser
A J
AJ
Department of Surgery, UCLA School of Medicine, Los Angeles, California.
Abedin
M Z
MZ
Cates
J A
JA
Giurgiu
D I
DI
Karam
J A
JA
Roslyn
J J
JJ
D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism; D002769:Cholelithiasis / Q000378:metabolism; D000242:Cyclic AMP / Q000502:physiology; D004285:Dogs; D005704:Gallbladder / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D012964:Sodium / Q000378:metabolism
D002712:Chlorides; D000001:Calcimycin; D012964:Sodium; D000242:Cyclic AMP; D002118:Calcium; D007213:Indomethacin