Differential Regulation of Leptin Transport by the Choroid Plexus and Blood-Brain Barrier and High Affinity Transport Systems for Entry into Hypothalamus and Across the Blood-Cerebrospinal Fluid Barrier*
| Autor: | Wesley Miao, Shea Samara, Suzana Jovanovic, Berislav V. Zlokovic, Sunil P. Verma, Catherine L. Farrell |
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| Rok vydání: | 2000 |
| Předmět: |
Leptin
Male medicine.medical_specialty Central nervous system Hypothalamus Blood–brain barrier Binding Competitive Energy homeostasis Endocrinology Internal medicine medicine Animals Rats Wistar biology Membrane transport protein digestive oral and skin physiology Biological Transport Rats Kinetics medicine.anatomical_structure Blood-Brain Barrier Cerebral cortex Choroid Plexus biology.protein Choroid plexus Carrier Proteins hormones hormone substitutes and hormone antagonists |
| Zdroj: | Endocrinology. 141:1434-1441 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/endo.141.4.7435 |
| Popis: | Leptin is a circulating hormone that controls food intake and energy homeostasis. Little is known about leptin entry into the central nervous system (CNS). The blood-cerebrospinal fluid (CSF) barrier at the choroid plexus and the blood-brain barrier (BBB) at the cerebral endothelium are two major controlling sites for entry of circulating proteins into the brain. In the present study, we characterized leptin transport across the blood-CSF barrier and the BBB by using a brain perfusion model in lean rats. Rapid, high-affinity transport systems mediated leptin uptake by the hypothalamus (KM = 0.2 ng/ml) and across the blood-CSF barrier (KM = 1.1 ng/ml). High affinity in vivo binding of leptin was also detected in the choroid plexus (KD = 2.6 ng/ml). In contrast, low affinity carriers for leptin (KM = 88 to 345 ng/ml) were found at the BBB in the CNS regions outside the hypothalamus (e.g. cerebral cortex, caudate nucleus, hippocampus). Our findings suggest a key role of high affinity leptin transporters in the hypothalamus and choroid plexus in regulating leptin entry into the CNS and CSF under physiological conditions. Low affinity transporters at the BBB outside the hypothalamus could potentially contribute to overall neuropharmacological effects of exogenous leptin. |
| Databáze: | OpenAIRE |
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