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Cholecystokinin peptides in cerebrospinal fluid: a study in healthy male subjects
Department of Clinical Neuroscience and Family Medicine, Division of Psychiatry, Karolinska Institute, Huddinge Hospital, Sweden.
Department of Clinical Neuroscience and Family Medicine, Division of Psychiatry, Karolinska Institute, Huddinge Hospital, Sweden.
Department of Internal Medicine, Karolinska Institute, Huddinge Hospital, Sweden.
Clinical Research Center, Novum, Karolinska Institute, Huddinge Hospital, Sweden.
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1997 (English)In: Regulatory Peptides, ISSN 0167-0115, E-ISSN 1873-1686, Vol. 68, no 1, 57-61 p.Article in journal (Refereed) Published
Abstract [en]

The clinical reliability of measuring cholecystokinin (CCK) peptides in the cerebrospinal fluid (CSF) has not been fully elucidated. Therefore, we have assayed CCK-8S and CCK-4 in CSF obtained from 14 healthy male subjects, lumbar-punctured at the L4–5 level following a strictly standardised procedure. CSF concentrations of free CCK-8S and free CCK-4 were used as dependent variables while age, height, body weight, atmospheric pressure and some other factors served as independent variables. It was shown that the CCK-8S ratio between the second (7–12 ml) and first (0–6 ml) CSF fractions, correlated significantly with the atmospheric pressure at the time of puncture. Neither CCK-8S nor CCK-4 displayed concentration gradients in CSF. The CCK-4 levels, expressed as pmol l−1 in the total amount of CSF were found to be positively correlated with the neuraxis distance in the lying position and negatively with the neuraxis distance in the sitting position. Furthermore, CCK-4, expressed as pmol l−1 per min of tapping-time (pmol l−1 min−1), showed a negative correlation with storage time, presumably mirroring a proteolytic process. CCK-8S and CCK-4 intercorrelated positively independently of whether expressed as pmol l−1 or pmol l−1 min−1. In conclusion, the results of this exploratory study indicate that the neuraxis distance (in the sitting and lying positions) and storage-time have to be accounted for when interpreting data on CSF levels of CCK-4. Attention has to be paid to the potential influence of atmospheric pressure on the concentration ratio of CCK-8S.

Place, publisher, year, edition, pages
1997. Vol. 68, no 1, 57-61 p.
Keyword [en]
CCK-4, CCK-8S, Atmospheric pressure, Storage-time, Tapping-time
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:liu:diva-79854DOI: 10.1016/S0167-0115(96)02104-0OAI: oai:DiVA.org:liu-79854DiVA: diva2:544436
Available from: 2012-08-14 Created: 2012-08-14 Last updated: 2017-12-07Bibliographically approved
In thesis
1. On the cerebrospinal fluid disposition and neurobiological role of cholecystokinin in man
Open this publication in new window or tab >>On the cerebrospinal fluid disposition and neurobiological role of cholecystokinin in man
2000 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Cholecystokinin (CCK) is the most abundant neuropeptide in the brain, where it acts as a neurotransmitter and neuromodulator. The tetrapeptide CCK-4 and the octapeptide CCK-8 have been implicated in various behavioural and physiological functions, such as anxiety, pain and satiety. Analyses of the levels of CCK in plasma, CSF and brain tissue have been used in studies aimed at elucidating the pathophysiological mechanisms in psychiatric disorders, but the results have been inconsistent.

Cerebrospinal fluid (CSF) levels of CCK-4 and CCK-8S were analysed in three groups of healthy subjects lumbar-punctured under different conditions, with the aim to provide reference values for studies on patients, and to investigate putative confounding factors. It was found that the concentrations of CCK-4 and CCK-8S were influenced by age, bedrest or not prior to lumbar puncture, neuraxis distance, position during lumbar puncture, height, atmospheric pressure and storage time. For a correct interpretation of data, these factors should be taken into account in future CSF studies in volunteers and patients.

Hypothyroidism is associated with depression. Thyroid hormones have been assumed to affect neuronal functions in the CNS, and animal experiments have indicated a relationship between thyroid hormones and CCK. Depressive symptoms were assessed in hypothyroid patients who were also lumbar-punctured before and during L-thyroxine treatment. Thyroid stimulating hormone, tri-iodothyronine and thyroxine in serum correlated with both CCK peptides in the CSF. A negative correlation between CCK-4 and inner tension (anxiety) was found.

Various studies implicate the involvement of brain-stem structures in the aetiology of panic attacks. Brain-stem auditory evoked potentials were recorded in healthy subjects before and during infusion with the panic-provoking agent CCK-4 or placebo. CCK-4 delayed the latencies of peak I, III and V, and decreased peak III amplitude. This suggests that exogenous CCK-4 affects stimulus processing in the brain stem.

Place, publisher, year, edition, pages
Linköping: Linköpings universitet, 2000. 70 p.
Series
Linköping University Medical Dissertations, ISSN 0345-0082 ; 643
National Category
Medical and Health Sciences
Identifiers
urn:nbn:se:liu:diva-28039 (URN)12800 (Local ID)91-7219-744-7 (ISBN)12800 (Archive number)12800 (OAI)
Public defence
2000-10-20, Berzeliussalen, Hälsouniversitetet, Linköping, 09:00 (Swedish)
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Supervisors
Available from: 2009-10-08 Created: 2009-10-08 Last updated: 2012-08-14Bibliographically approved

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