THE EFFECT OF THE CHOLECYSTOKININ RECEPTOR ANTAGONIST MK-329 ON MEAL-STIMULATED PANCREATICOBILIARY OUTPUT IN HUMANS

被引:56
作者
CANTOR, P
MORTENSEN, PE
MYHRE, J
GJORUP, I
WORNING, H
STAHL, E
SURVILL, TT
机构
[1] RIGSHOSP,DEPT CLIN CHEM & SURG GASTROENTEROL C,DK-2100 COPENHAGEN,DENMARK
[2] GLOSTRUP UNIV HOSP,DEPT MED GASTROENTEROL,GLOSTRUP,DENMARK
关键词
D O I
10.1016/0016-5085(92)91738-P
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
To determine the physiological role of circulating cholecystokinin (CCK), the effect of the CCK receptor antagonist MK-329 on upper digestive processes was investigated in six normal volunteers after a mixed meal. In a double-blind, two-period, randomized crossover design, the subjects received either 10 mg MK-329 or placebo orally 3 hours 15 minutes before the meal, which contained 51CrCl3 as food marker. A five-lumen tube with the tip in the distal duodenum allowed continuous marker infusion (57Co-B12) and duodenal aspiration as well as recordings of antral and duodenal motility patterns via three pressure sensors. Postprandially, MK-329 caused a significant reduction of 30%-60% (P < 0.05) in pancreatic trypsin output during the initial three 15-minute periods; thereafter, the output was virtually the same than after placebo. Thus, the integrated enzyme response was only reduced by 15% (NS) during the 3-hour period beginning 15 minutes after the meal. In contrast, gallbladder contraction, determined by total bile acid excretion, was inhibited by 77% (P < 0.05), indicating a crucial role of CCK in regulating gallbladder motility. Except for the initial 30 minutes postprandially, MK-329 also induced a significant reduction in duodenal pH with mean values ranging from 3.5 ± 0.2 to 4.1 ± 0.3 compared with 4.5 ± 0.3 to 5.0 ± 0.4 after placebo (P < 0.05), probably because of lowered secretion of pancreatic bicarbonate. Gastric emptying rate was significantly accelerated by MK-329 during the initial 75 minutes after the meal, but the time for 50% emptying did not differ from placebo [127.5 ± 7.7 vs. 140.0 ± 9.0 minutes (NS)]. No changes were observed in the motility pattern of the proximal duodenum after feeding. Whereas MK-329 only caused a slight increase of the basal plasma CCK concentrations, the postprandial levels were markedly enhanced. Peak concentrations were 10.0 ± 1.3 vs. 4.0 ± 0.5 pmol/L after placebo (P < 0.001), and the integrated response exceeded the control value by 175% (P < 0.01). The results suggest that circulating CCK is not an essential mediator of the postprandial pancreatic enzyme secretion in humans, whereas it plays a critical role in gallbladder emptying. © 1992.
引用
收藏
页码:1742 / 1751
页数:10
相关论文
共 43 条
  • [21] DO BILE-ACIDS EXERT A NEGATIVE FEEDBACK-CONTROL OF CHOLECYSTOKININ RELEASE
    KOOP, I
    KOOP, H
    GERHARDT, C
    SCHAFMAYER, A
    ARNOLD, R
    [J]. SCANDINAVIAN JOURNAL OF GASTROENTEROLOGY, 1989, 24 (03) : 315 - 320
  • [22] REGULATION OF GASTRIC-EMPTYING IN HUMANS BY CHOLECYSTOKININ
    LIDDLE, RA
    MORITA, ET
    CONRAD, CK
    WILLIAMS, JA
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1986, 77 (03) : 992 - 996
  • [23] EFFECTS OF A NOVEL CHOLECYSTOKININ (CCK) RECEPTOR ANTAGONIST, MK-329, ON GALLBLADDER CONTRACTION AND GASTRIC-EMPTYING IN HUMANS - IMPLICATIONS FOR THE PHYSIOLOGY OF CCK
    LIDDLE, RA
    GERTZ, BJ
    KANAYAMA, S
    BECCARIA, L
    COKER, LD
    TURNBULL, TA
    MORITA, ET
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1989, 84 (04) : 1220 - 1225
  • [24] CHOLECYSTOKININ BIOACTIVITY IN HUMAN-PLASMA - MOLECULAR-FORMS, RESPONSES TO FEEDING, AND RELATIONSHIP TO GALLBLADDER CONTRACTION
    LIDDLE, RA
    GOLDFINE, ID
    ROSEN, MS
    TAPLITZ, RA
    WILLIAMS, JA
    [J]. JOURNAL OF CLINICAL INVESTIGATION, 1985, 75 (04) : 1144 - 1152
  • [25] LOTTI VJ, 1987, J PHARMACOL EXP THER, V241, P103
  • [26] A CHOLECYSTOKININ RELEASING PEPTIDE MEDIATES FEEDBACK-REGULATION OF PANCREATIC-SECRETION
    LU, L
    LOUIE, D
    OWYANG, C
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1989, 256 (02): : G430 - G435
  • [27] MAKOVEC F, 1987, ARZNEIM FORSCH DRUG, V37, P1235
  • [28] SCINTIGRAPHIC EVALUATION OF GASTRIC-EMPTYING
    MALMUD, LS
    FISHER, RS
    KNIGHT, LC
    ROCK, E
    [J]. SEMINARS IN NUCLEAR MEDICINE, 1982, 12 (02) : 116 - 125
  • [29] ROLE OF CHOLECYSTOKININ IN REGULATION OF GASTROINTESTINAL MOTOR FUNCTIONS
    MEYER, BM
    WERTH, BA
    BEGLINGER, C
    HILDEBRAND, P
    JANSEN, JBMJ
    ZACH, D
    ROVATI, LC
    STADLER, GA
    [J]. LANCET, 1989, 2 (8653) : 12 - 15
  • [30] MINAMI H, 1984, GASTROENTEROLOGY, V86, P1592