TY - JOUR
T1 - Effect of three nonpeptide cholecystokinin antagonists on human isolated gallbladder
AU - Maselli, M. A.
AU - Piepoli, A. L.
AU - Pezzolla, F.
AU - Guerra, V.
AU - Caruso, M. L.
AU - Mennuni, L.
AU - Lorusso, D.
AU - Makovec, F.
PY - 2001
Y1 - 2001
N2 - Cholecystokinin is the most important stimulant of postprandial gallbladder contraction, and a regulator of gallbladder fasting tone. The aim of this study was to evaluate the effect of dexloxiglumide on isolated human gallbladder contraction induced by cholecystokinin-octapeptide and to compare this effect to that of lorglumide and amiglumide, two glutaramic acid analogs of dexloxiglumide. The negative logarithms of the antagonist dissociation constant (pK
B) values were 7.00 ± 0.14, 6.95 ± 0.11, and 6.71 ± 0.10 for lorglumide, dexloxiglumide, and amiglumide, respectively. Dexloxiglumide produced a concentration-dependent rightward shift of the cholecystokinin-octapeptide curve, without affecting its maximal response. A similar effect was obtained both with lorglumide and amiglumide. Moreover, the slopes for the three antagonists did not differ significantly from unity. These data show that the three molecules have a potent antagonistic effect, of a competitive nature, on gallbladder cholecystokinin type 1 receptors. It may be concluded that dexloxiglumide, lorglumide, and amiglumide exhibit a promising therapeutic profile for biliary colic and other gastrointestinal disorders in which CCK
1 receptors play important physiological roles.
AB - Cholecystokinin is the most important stimulant of postprandial gallbladder contraction, and a regulator of gallbladder fasting tone. The aim of this study was to evaluate the effect of dexloxiglumide on isolated human gallbladder contraction induced by cholecystokinin-octapeptide and to compare this effect to that of lorglumide and amiglumide, two glutaramic acid analogs of dexloxiglumide. The negative logarithms of the antagonist dissociation constant (pK
B) values were 7.00 ± 0.14, 6.95 ± 0.11, and 6.71 ± 0.10 for lorglumide, dexloxiglumide, and amiglumide, respectively. Dexloxiglumide produced a concentration-dependent rightward shift of the cholecystokinin-octapeptide curve, without affecting its maximal response. A similar effect was obtained both with lorglumide and amiglumide. Moreover, the slopes for the three antagonists did not differ significantly from unity. These data show that the three molecules have a potent antagonistic effect, of a competitive nature, on gallbladder cholecystokinin type 1 receptors. It may be concluded that dexloxiglumide, lorglumide, and amiglumide exhibit a promising therapeutic profile for biliary colic and other gastrointestinal disorders in which CCK
1 receptors play important physiological roles.
KW - Cholecystokinin antagonists
KW - Dexloxiglumide
KW - Gallbladder motility
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U2 - 10.1023/A:1012748017709
DO - 10.1023/A:1012748017709
M3 - Article
C2 - 11768273
AN - SCOPUS:0035211557
VL - 46
SP - 2773
EP - 2778
JO - Digestive Diseases and Sciences
JF - Digestive Diseases and Sciences
SN - 0163-2116
IS - 12
ER -