Effect of three nonpeptide cholecystokinin antagonists on human isolated gallbladder

M. A. Maselli, A. L. Piepoli, F. Pezzolla, V. Guerra, M. L. Caruso, L. Mennuni, D. Lorusso, F. Makovec

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)2773-2778
Number of pages6
JournalDigestive Diseases and Sciences
Volume46
Issue number12
DOIs
Publication statusPublished - 2001

Keywords

  • Cholecystokinin antagonists
  • Dexloxiglumide
  • Gallbladder motility

ASJC Scopus subject areas

  • Gastroenterology

Fingerprint Dive into the research topics of 'Effect of three nonpeptide cholecystokinin antagonists on human isolated gallbladder'. Together they form a unique fingerprint.

Cite this