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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 
 
 
 
 

Effect of three nonpeptide cholecystokinin antagonists on human isolated gallbladder.

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 CCK1 receptors play important physiological roles.[1]

References

  1. Effect of three nonpeptide cholecystokinin antagonists on human isolated gallbladder. Maselli, M.A., Piepoli, A.L., Pezzolla, F., Guerra, V., Caruso, M.L., Mennuni, L., Lorusso, D., Makovec, F. Dig. Dis. Sci. (2001) [Pubmed]
 
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