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μ ‐Opiate receptor agonist loperamide blocks bethanechol‐induced gallbladder contraction, despite higher cholecystokinin plasma levels in man
Author(s) -
Otto B.,
Mawe G. M.,
Riepl R. L.
Publication year - 2005
Publication title -
neurogastroenterology and motility
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.489
H-Index - 105
eISSN - 1365-2982
pISSN - 1350-1925
DOI - 10.1111/j.1365-2982.2005.00694.x
Subject(s) - bethanechol , loperamide , endocrinology , motilin , medicine , cholecystokinin , agonist , chemistry , receptor , muscarinic acetylcholine receptor , diarrhea
μ ‐Opiate receptor agonists, such as loperamide, influence biliary excretion and suppress cholecystokinin (CCK)‐induced gallbladder contraction. Loperamide decreases cholinergic mechanisms, like pancreatic polypeptide (PP) release, while muscarinic agonist (bethanechol)‐induced PP release remains unaffected. The effects of loperamide on gallbladder contraction and peptide release were performed to resolve this discrepancy. Methods: Six subjects (27.6 ± 2.0 years) received bethanechol (12.5, 25 and 50 μ g kg −1 h −1 continuously over 40 min) after oral 16 mg loperamide ( vs placebo) in a crossover design. Gallbladder volume and plasma levels of CCK, PP, motilin, gastrin, neurotensin, cholylglycine were measured regularly. Results: Bethanechol significantly reduced gallbladder volume (26.7 ± 1.9 to a nadir of 15.3 ± 2.2 mL, P ≤ 0.05), and this action was inhibited by loperamide. Basal CCK levels increased significantly after loperamide. Incremental integrated CCK release after bethanechol was higher under loperamide ( P ≤ 0.05), as placebo CCK release was significantly decreased under bethanechol (2.0 ± 0.4–0.8 ± 0.3 pmol L −1 ). In both settings, PP levels were significantly increased after bethanechol, while release of neurotensin, motilin, gastrin and cholylglycine was unaffected. Conclusion: The μ ‐opiate receptor agonist loperamide inhibits bethanechol‐induced gallbladder contraction. This effect is not mediated by inhibition of CCK release, as loperamide even enhances basal CCK plasma levels. As cholinergic mechanisms, like bethanechol‐induced incremental PP release, were unaffected, μ ‐opiate agonists might influence gallbladder contraction via vagal–cholinergic pathways.