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Characterization of Dextromethorphan And Dextrorphan Uptake by a Putative Glutamic Acid Carrier and Passive Diffusion Across Brain Microvessel Endothelium
dc.contributor.author | Shi, Fenglin | |
dc.contributor.author | Cavitt, Jennifer | |
dc.contributor.author | Bailey, Carole A. | |
dc.contributor.author | Malick, Waseem A. | |
dc.contributor.author | Audus, Kenneth L. | |
dc.date.accessioned | 2011-06-16T16:38:26Z | |
dc.date.available | 2011-06-16T16:38:26Z | |
dc.date.issued | 1993 | |
dc.identifier.citation | Shi, F., Cavitt, J.L., Bailey, C., Malick, A.W., and Audus, K.L. (1993) Characterization of dextromethorphan and dextrorphan uptake by a putative glutamic acid carrier and passive diffusion across brain microvessel endothelium. Drug Delivery 1, 113-118. http://dx.doi.org/10.3109/10717549309022764 | |
dc.identifier.uri | http://hdl.handle.net/1808/7612 | |
dc.description | Read More: http://informahealthcare.com/doi/abs/10.3109/10717549309022764 | |
dc.description.abstract | The mechanisms of uptake and transcellular passage of dextromethorphan (DM) and its major metabolite dextrorphan (DX) across the endothelial component of the blood–brain barrier have been investigated with primary cultures of bovine brain microvessel endothelial cells (BMECs). The uptake of [14C]DM and [14C]DX by BMECs was observed to be temperature-sensitive and saturable, with approximate Km's of 0.12 and 0.29 mM and Vmax's of 9.2 and 11.0 pmol/mg/min, respectively. The BMEC uptake of [14C] DM was inhibited half-maximally by approximately 0.57 mM L-glutamic acid, 0.71 mM N-methyl-d-asparatate (NMDA), and 0.99 mM DL-threo-β-hydroxyaspartic acid. The BMEC uptake of [14C]DX was inhibited half-maximally by approximately 0.48 mM L-glutamic acid, 1.50 mM NMDA, and 0.69 mM DL-threo-β-hydroxyaspartic acid. Conversely, the bidirectional passage of DM and DX across confluent BMEC monolayers occurred at a faster rate but was neither saturable nor inhibited by high concentrations of glutamic acid, NMDA, or unlabeled DM or DX. These results suggest that DM and DX are capable of interacting with a low-capacity glutamic acid-type carrier mechanism on the apical surface of BMECs. However, the net transfer of these agents across BMEC monolayers appeared to be more rapid and passive in nature. | |
dc.language.iso | en_US | |
dc.publisher | Informa Healthcare | |
dc.title | Characterization of Dextromethorphan And Dextrorphan Uptake by a Putative Glutamic Acid Carrier and Passive Diffusion Across Brain Microvessel Endothelium | |
dc.type | Article | |
kusw.kuauthor | Audus, Kenneth L. | |
kusw.kudepartment | Pharmacy | |
kusw.oastatus | fullparticipation | |
dc.identifier.doi | 10.3109/10717549309022764 | |
kusw.oaversion | Scholarly/refereed, publisher version | |
kusw.oapolicy | This item meets KU Open Access policy criteria. | |
dc.rights.accessrights | openAccess |
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Pharmacy Scholarly Works [299]