Cholecystokinin, or "CCK" peptides, originally identified in the gastrointestinal tract, are now considered to be one of the most abundant peptide systems in the mammalian central nervous system. Prompted by recent findings that implicated the cholecystokinergic system in the pathophysiology of various illnesses, we developed a novel assay system to measure the various forms of cholecystokinin peptides in human plasma and cerebrospinal fluid. The system detects CCK-4, sulfated CCK-8 (CCK-8s) and nonsulfated CCK-8 (CCK-8ns) with equal affinity, with the lower detection limit of 2.7 fmol and an ED50 of 10.6 +/- 2.2 fmol. Using the assay system, we determined that mean CCK-like immunoreactivity (CCK-LI) in the plasma of 12 healthy subjects was 12.9 +/- 2.1 pM CCK-4 equivalents. / After developing the cholecystokinin assay system, we were able to combine our unique methodology with other established techniques to investigate the role of CCK in illnesses such as premenstrual dysphoric disorder (PMDD), anxiety, bulimia nervosa, and cardiomyopathy. / Briefly, we observed no significant differences in plasma CCK levels between women with PMDD and healthy volunteers. However, we found that, independent of diagnosis, plasma cholecystokinin concentrations were higher in women during their first visit to the clinic to participate in the study, as compared to later visits. / In addition, application of our assay system allowed us to determine that oral ingestion of caffeine increased plasma CCK-LI levels 2--4 fold in humans. Moreover, we observed substantial variation in post-caffeine cholecystokinin levels among individuals. / In another study of cholecystokinin and anxiety, we used our CCK assay to determine the effects of ondansetron, a serotonin receptor antagonist, on cholecystokinin levels in plasma. We found that multiple oral doses of ondansetron influence the pharmacokinetic parameters of exogenous CCK. / We also used the three-step assay system to measure CCK-LI in patients with the eating disorder, bulimia nervosa. Baseline fasted cholecystokinin plasma levels were lower in bulimic women as compared to control subjects. However, at "satiety", or the post-binge stage, CCK levels in bulimic women were similar to those of control women. / Finally, our investigation into the role of cholecystokinin in cardiomyopathy revealed that neuronal cholecystokinin receptor density was altered in the cardiomyopathic hamster brain, as compared to age- and sex-matched control animals. (Abstract shortened by UMI.)
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:QMM.37619 |
| Date | January 2001 |
| Creators | Merani, Salima A. |
| Contributors | Palmour, Roberta (advisor) |
| Publisher | McGill University |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Electronic Thesis or Dissertation |
| Format | application/pdf |
| Coverage | Doctor of Philosophy (Department of Biology.) |
| Rights | All items in eScholarship@McGill are protected by copyright with all rights reserved unless otherwise indicated. |
| Relation | alephsysno: 001807036, proquestno: NQ70099, Theses scanned by UMI/ProQuest. |
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