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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Drewe, J. Huwyler, J. Klusemann, C. Fricker, G. |
| Description | Author Affiliation: Huwyler J ( Dept. of Anaesthesia and Research, University Hospital, Basel, Switzerland.) |
| Abstract | 1. Morphine-6-glucuronide is one of the major metabolites of morphine. The potent analgesic action of this compound together with its potential lower apparent toxicity in man, when compared with morphine, indicated its clinical importance. 2. Primary cultures of porcine brain capillary endothelial cells were used to study brain penetration of morphine-6-glucuronide. Biochemical characterization of the cell cultures revealed a marked enrichment in enzymatic activity of alkaline phosphatase (56 fold) and angiotensin converting enzyme (230 fold) as compared to whole brain tissue. By immunostaining the presence of vimentin, factor VIII, the tight junction associated protein ZO-1, and P-glycoprotein was shown. Functional characterization revealed that the carrier system responsible for transport of neutral amino acids was intact. 3. Uptake and transport of morphine-6-glucuronide was marginal and in the range of the extracellular marker sucrose. However, uptake of morphine-6-glucuronide was enhanced significantly (P < 0.0001) in presence of the inhibitors of P-glycoprotein, verapamil or vincristine. The finding that morphine-6-glucuronide may serve as a substrate for P-glycoprotein was confirmed in multidrug-resistant P388 tumour cells. 4. We conclude that penetration of the blood-brain barrier by morphine-6-glucuronide may depend on the expression of the product of the multidrug-resistance (MDR) gene in brain capillary endothelial cells. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 8 |
| Volume Number | 118 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 1996-08-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Brain Drug Effects Cerebrovascular Circulation Morphine Derivatives Metabolism P-Glycoprotein Pharmacology Animals Capillaries Cells, Cultured Immunohistochemistry Swine Research Support, Non-U.S. Gov't |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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