THE ROLE OF CHOLECYSTOKININ AND THE CHOLINERGIC SYSTEM IN INTRAVENOUSAMINO ACID-INDUCED GALLBLADDER EMPTYING

Background: Recent studies have demonstrated that separate intravenous infusion of amino acids (IVAA) at high doses induces gallbladder empt ying. However, little is known about the mechanisms mediating IVAA-ind uced gallbladder contraction. Objective and methods: To investigate wh ether the effect of IVAA on gallbladder motility is mediated by the ch olinergic system and/or cholecystokinin (CCK), the major hormonal stim ulus for gallbladder contraction. Six healthy male volunteers were stu died in random order on five occasions using: (a) IVAA, (b) loxiglumid e (CR 1505, a selective CCK-A receptor antagonist), (c) IVAA plus loxi glumide, (d) atropine and (e) IVAA plus atropine. Gallbladder volumes (ultrasonography) and plasma CCK levels (radioimmunoassay) were determ ined every 15 min for 60 min before and for 120 min during intravenous infusion of amino acids (Vamin 18EF; 250 mg protein/kg/h) and/or loxi glumide (10 mg/kg/h) and/or atropine (0.005 mg/kg/h). Results: IVAA si gnificantly (P < 0.05) reduced gallbladder volume from 32 +/- 5 ml to 17 +/- 2 ml but induced only a small and transient increase in plasma CCK levels. Loxiglumide given alone significantly (P < 0.05) increased fasting gallbladder volume to 190% of the basal value. IVAA-induced g allbladder emptying was completely abolished by loxiglumide. Maximal g allbladder relaxation during IVAA plus loxiglumide was not significant ly different compared to loxiglumide given alone. Concomitant administ ration of atropine also significantly (P < 0.05) inhibited IVAA-induce d gallbladder emptying. Conclusion: In healthy volunteers intravenous infusion of high doses of amino acids results in a significant gallbla dder contraction, which is inhibited by CCK-A receptor blockade and by atropine.