A cholecystokinin‐1 receptor agonist (CCK‐8) mediates increased permeability of brain barriers to leptin

Background and purpose: Leptin regulates energy expenditure and body weight by acting both on the hypothalamus and on peripheral targets. Central actions of leptin are enhanced by cholecystokinin (CCK). The interaction between leptin and CCK makes physiological sense, as rats lacking CCK1 receptors...

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Bibliographic Details
Published in:British journal of pharmacology 2008-07, Vol.154 (5), p.1009-1015
Main Authors: Cano, V, Merino, B, Ezquerra, L, Somoza, B, Ruiz‐Gayo, M
Format: Article
Language:English
Subjects:
Animals
Benzodiazepinones - pharmacology
Biological and medical sciences
Blood Glucose - metabolism
Blood-Brain Barrier - drug effects
Blood-Brain Barrier - metabolism
blood–brain barrier
CCK1 receptor
Cell Membrane Permeability - drug effects
cholecystokinin
choroid plexus
Eating
hypothalamus
Indoleacetic Acids - pharmacology
Injections, Intraperitoneal
Insulin - blood
Kinetics
leptin
Leptin - administration & dosage
Leptin - blood
Leptin - cerebrospinal fluid
Leptin - metabolism
leptin transport
Male
Medical sciences
Pharmacology. Drug treatments
Phenylurea Compounds - pharmacology
Rats
Rats, Sprague-Dawley
Receptors, Cholecystokinin - agonists
Receptors, Cholecystokinin - metabolism
Recombinant Proteins - metabolism
Research Papers
Sincalide - administration & dosage
Sincalide - metabolism
SR‐27,897
Thiazoles - pharmacology
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Summary:Background and purpose: Leptin regulates energy expenditure and body weight by acting both on the hypothalamus and on peripheral targets. Central actions of leptin are enhanced by cholecystokinin (CCK). The interaction between leptin and CCK makes physiological sense, as rats lacking CCK1 receptors are resistant to peripheral leptin but not to leptin directly infused into the brain. We have recently reported that CCK enhances leptin effects by increasing the entry of leptin into the CNS. The aim of this work was to further characterize the effect of CCK (10 μg kg−1) on leptin kinetics as well as the CCK receptor subtype involved in the interaction between CCK and leptin. Experimental approach: Experiments were carried out both in free‐feeding and in fasted rats receiving a single dose of leptin (100 μg kg−1; i.p.). Parameters analysed over the next 6 h were plasma and cerebrospinal fluid concentrations of leptin. Key results: We observed that CCK‐8 depressed the increase in plasma leptin that followed the i.p. injection and simultaneously increased leptin concentration in the cerebrospinal fluid from 92±25 to 230±24 pg mL−1 (P
ISSN:0007-1188
1476-5381
DOI:10.1038/bjp.2008.149