Enhanced cerebral uptake of receptor ligands by modulation of P-glycoprotein function in the blood-brain barrier
| Autor: | Philippus Elsinga, P Doze, NH Hendrikse, W Vaalburg, van Aren Waarde |
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| Přispěvatelé: | Clinical pharmacology and pharmacy, Guided Treatment in Optimal Selected Cancer Patients (GUTS) |
| Jazyk: | angličtina |
| Rok vydání: | 2000 |
| Předmět: |
BETA-ADRENERGIC-RECEPTOR
Adrenergic receptor beta-adrenoceptors Pharmacology P-glycoprotein Blood–brain barrier RAT-BRAIN Cellular and Molecular Neuroscience Cyclosporin a BINDING medicine ABSORPTION Distribution (pharmacology) DRUGS MULTIDRUG-RESISTANCE Receptor biology Chemistry blood-brain barrier GENE TRANSPORT medicine.anatomical_structure PET LIPOPHILICITY Knockout mouse biology.protein SECRETION Efflux |
| Zdroj: | SYNAPSE, 36(1), 66-74. Wiley-Liss Inc. Doze, P, Van Waarde, A, Elsinga, P H, Hendrikse, N H & Vaalburg, W 2000, ' Enhanced cerebral uptake of receptor ligands by modulation of P-glycoprotein function in the blood-brain barrier ', SYNAPSE, vol. 36, no. 1, pp. 66-74 . https://doi.org/10.1002/(SICI)1098-2396(200004)36:1<66::AID-SYN7>3.0.CO;2-J Synapse, 36(1), 66-74. WILEY-LISS |
| ISSN: | 0887-4476 |
| DOI: | 10.1002/(SICI)1098-2396(200004)36:1<66::AID-SYN7>3.0.CO;2-J |
| Popis: | Low cerebral uptake of some therapeutic drugs can be enhanced by modulation of P-glycoprotein (P-gp), an ATP-driven drug efflux pump at the blood-brain barrier (BBB). We investigated the possibility of increasing cerebral uptake of the β-adrenergic ligands S-1'-[18F]-fluorocarazolol (FCAR) and [11C]-carazolol (CAR) in P-gp knockout mice (mdr1a (-/-)) and by modulation of P-gp with cyclosporin A (CsA) in rats. Specific and nonspecific binding of FCAR in the rat brain were doubled by CsA, while target/nontarget ratios and clearance from plasma (area under curve (AUG)) were not affected. Cerebral uptake of CAR in rats was much lower than FCAR and nonspecific. CsA increased this uptake 5-6-fold, not only due to P-gp modulation in the BBB but also to a 2-fold higher plasma AUG. In the CNS of mdr1a (-/-) mice, uptake of FCAR and CAR was, respectively, 2-fold and 3-fold higher than in mdr1a (+/+) mice. These results indicate that the cerebral uptake of β- adrenoceptor ligands can be increased by administration of P-gp modulators such as CsA without affecting regional distribution in the brain. P-gp modulation could improve the count statistics in PET studies of the CNS. (C) 2000 Wiley-Liss, Inc. |
| Databáze: | OpenAIRE |
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