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Effect of a physiologic dose of cholecystokinin on food intake and satiation in man
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EFFECT OF A PHYSIOLOGIC DOSE OF CHOLECYSTOKININ ON FOOD INTAKE AND SATIATION IN MAN. R. Lieverse, J. Jansen, A. van de Zwan, L. Samson, A. Masclee, C. Lamers. Dept. Gastroenterology-Hepatology, University Hospital Leiden, The Netherlands. Introduction: Many studies have demonstrated that cholecystokinin (CCK) reduces food intake in several species including humans. In these human studies, however, plasma CCK levels were not measured and may well have been in the supraphysiological range. Aim: In this study we investigated if an infusion leading to high physiologic plasma levels of CCK also stimulates satiation in lean and/or obese humans. Methods: 18 healthy humans, 9 lean J,5F, 4M, mean age 29, range 22-36, with a mean body mass index (BMI) of 22 (20-25) kg/m ~) ando9 obese (9F, mean age 40, range 30-59, with a mean body man index of 40 (33-49) kg/m =) were studied. In a double blind fashion they received after an overnight fast either saline i.v. or CCK-33 (2.5 IDU/kg ideal weight.150 min, Kabi Vitrium®, Sweden). Sixty minutes after the start of the infusions an identical meal consisting of banana slices which in itself does not stimulate CCK release was presented and each subject was free to eat as much as wanted. Feelings for hunger and fullness were scored. Results: During CCK infusion food intake (486+52 g, (mean+SEM)), was slightly, although not significantly, less than during saline infusion (553+55 g, p=0.09). Hunger and fullness feelings after eating were also not significantly affected by CCK. Looking at separate groups CCK had neither in lean nor in obese humans a significant effect on food intake nor on hunger and fullness feelings. Infusion of CCK resulted in significant increases of plasma CCK concentrations stabilizing within 60 min of infusion at values fluctuating around 12 pM comparable to those found after a fatty meal. Conclusion: Under the conditions of this study there is no major effect of physiologic plasma levels of CCK on food intake and postprandial hunger feelings in lean or obese subjects.
C C K 8 Receptors in cells of the immune system : Characterization and transudction m e c h a n i s m . LIGNON M.F., BERNAD N., MARTINEZ J., CCIPE, Facult~ de Pharmacie, Montpellier CCK is both a gastrointestinal peptide and a neuropeptide and his regulatory functions in the immune system have been suggested by several studies. We have recently demonstrated the presence of C C K 8 binding sites in cells of the immune system. On a human Jurkat lymphoma cell line, 125I-BH-CCK8 bound to an apparently homogeneous population of h i g h a f f m i t y binding sites (Kd : 3.10-11M) displaying a typical pharmacological C C K - B - I i k e profile (central type receptor) r~f.(1). This cell line has been used for studying cellular events associated with receptor activation . We present evidence for a coupling of these C C K - B - I i k e receptors to a release of intracellular calcium (by use of a fluorescent probe Fura 2). C C K 8 induced in a dose dependent manner, an increase in cytoplasmic free calcium concentration. This response can be inhibited by use of specific CCK-B receptor antagonists and mimicked by CCK-B agonists. Further studies will be necessary to elucidate the physiological significance of these CCK-B receptors in these malignant lymphoid cell lines but this model may prove useful for studying CCK-B receptor trandusction mechanisms.
Ref.(1) - LIGNON M.F., BERNAD N., MARTINEZ J. Pharmacological characterization of Type B C h o l e c y s t o k i n i n binding sites on the human JURKAT T lymphocyte cell line, Molecular Pharmacology 39 : 615-620, 1991.
EFFECT OF A PHYSIOLOGIC DOSE OF CHOLECYSTOKININ ON FOOD INTAKE AND SATIATION IN MAN. R. Lieverse, J. Jansen, A. van de Zwan, L. Samson, A. Masclee, C. Lamers. Dept. Gastroenterology-Hepatology, University Hospital Leiden, The Netherlands. Introduction: Many studies have demonstrated that cholecystokinin (CCK) reduces food intake in several species including humans. In these human studies, however, plasma CCK levels were not measured and may well have been in the supraphysiological range. Aim: In this study we investigated if an infusion leading to high physiologic plasma levels of CCK also stimulates satiation in lean and/or obese humans. Methods: 18 healthy humans, 9 lean J,5F, 4M, mean age 29, range 22-36, with a mean body mass index (BMI) of 22 (20-25) kg/m ~) ando9 obese (9F, mean age 40, range 30-59, with a mean body man index of 40 (33-49) kg/m =) were studied. In a double blind fashion they received after an overnight fast either saline i.v. or CCK-33 (2.5 IDU/kg ideal weight.150 min, Kabi Vitrium®, Sweden). Sixty minutes after the start of the infusions an identical meal consisting of banana slices which in itself does not stimulate CCK release was presented and each subject was free to eat as much as wanted. Feelings for hunger and fullness were scored. Results: During CCK infusion food intake (486+52 g, (mean+SEM)), was slightly, although not significantly, less than during saline infusion (553+55 g, p=0.09). Hunger and fullness feelings after eating were also not significantly affected by CCK. Looking at separate groups CCK had neither in lean nor in obese humans a significant effect on food intake nor on hunger and fullness feelings. Infusion of CCK resulted in significant increases of plasma CCK concentrations stabilizing within 60 min of infusion at values fluctuating around 12 pM comparable to those found after a fatty meal. Conclusion: Under the conditions of this study there is no major effect of physiologic plasma levels of CCK on food intake and postprandial hunger feelings in lean or obese subjects.
C C K 8 Receptors in cells of the immune system : Characterization and transudction m e c h a n i s m . LIGNON M.F., BERNAD N., MARTINEZ J., CCIPE, Facult~ de Pharmacie, Montpellier CCK is both a gastrointestinal peptide and a neuropeptide and his regulatory functions in the immune system have been suggested by several studies. We have recently demonstrated the presence of C C K 8 binding sites in cells of the immune system. On a human Jurkat lymphoma cell line, 125I-BH-CCK8 bound to an apparently homogeneous population of h i g h a f f m i t y binding sites (Kd : 3.10-11M) displaying a typical pharmacological C C K - B - I i k e profile (central type receptor) r~f.(1). This cell line has been used for studying cellular events associated with receptor activation . We present evidence for a coupling of these C C K - B - I i k e receptors to a release of intracellular calcium (by use of a fluorescent probe Fura 2). C C K 8 induced in a dose dependent manner, an increase in cytoplasmic free calcium concentration. This response can be inhibited by use of specific CCK-B receptor antagonists and mimicked by CCK-B agonists. Further studies will be necessary to elucidate the physiological significance of these CCK-B receptors in these malignant lymphoid cell lines but this model may prove useful for studying CCK-B receptor trandusction mechanisms.
Ref.(1) - LIGNON M.F., BERNAD N., MARTINEZ J. Pharmacological characterization of Type B C h o l e c y s t o k i n i n binding sites on the human JURKAT T lymphocyte cell line, Molecular Pharmacology 39 : 615-620, 1991.