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Abstract
Background. Several studies examined in vivo and in vitro biologic activity of the human gallbladder
in response to cholecystokinin (CCK). However, few studies have demonstrated directly
the interaction of CCK with receptors on the human gallbladder, which is responsible
for this biologic activity.
Methods. To characterize CCK receptors on human gallbladder tissue, gallbladders were removed
from human donor grafts that were being used for liver transplantation. The gallbladders
were rapidly frozen and sectioned for measurement of binding of 125I-Bolton-Hunter-labeled-CCK-8 and were cut into strips for in vitro bioassay.
Results. Binding of 125I-BH-CCK-8 to human gallbladder was saturable, specific, and dependent on time, pH,
and temperature. The binding was inhibited only by cholecystokinin-related peptides
including CCK-8 (IC50 10 ± 1.0 nmol/L) (mean ± SD), des(S03) CCK-8 (IC50 0.9 ± 0.2 μmol/L), and gastrin-17-I (1C50 9.0 ± 2.0 μmol/L) or specific CCK receptor antagonist L-364,718. Computer analysis
of binding of 125I-BH-CCK-8 to gallbladder tissue showed a single class of binding sites with high
affinity for CCK-8. Autoradiography localized binding of 125I-BH-CCK-8 only to the smooth muscle layer of the gallbladder. In the bioassay des(S03) CCK-8 (EC50 1.2 ± 0.7 μmol/L) and gastrin-17-I (EC504.5 ± 2.4 μmol/L) were 150- and 563-fold less potent than CCK-8 (EC50 8.0 ± 2.2 nmol/L). The relative potencies of CCK agonists for inhibiting binding
of 125I-BH-CCK-8 agreed closely with their relative potencies for causing gallbladder contraction.
The dose-response curve for CCK-8 alone to induce gallbladder contraction was not
significantly different from those caused by CCK-8 plus 1 μmol/L tetrodotoxin or 1
μmol/L atropine.
Conclusions. These results characterized the CCK receptors on smooth muscle of human gallbladder
as sulfate dependent and causing gallbladder contraction.
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Article info
Publication history
Accepted:
October 24,
1991
Footnotes
☆Presented at the Ninety-first Annual Meeting of the American Gastroenterological Association, San Antonio, Texas, May 13–19, 1990.
Identification
Copyright
© 1993 Published by Elsevier Inc.
