Abstract
Uptake of drugs and other xenobiotics from the nasal cavity and into either the brain or systemic circulation can occur through several different mechanisms, including paracellular transport and movement along primary olfactory nerve axons, which extend from the nasal cavity to the olfactory bulb of the brain. The present study was conducted to expand knowledge on a third means of uptake, namely the expression of drug transporters in the rat nasal epithelium. We used branched DNA technology to compare the level of expression of nine transporters [(equilibrative nucleoside transporters (ENT)1 and ENT2; organic cation transporter (OCT)1, 2, and 3; OCTN1; organic anion-transporting polypeptide (OATP)3; and multidrug resistance (MRP)1 and MRP4] in nasal respiratory mucosa, olfactory mucosa, and olfactory bulb to the level of expression of these transporters in the liver and kidney. Transporters with high expression in the nasal respiratory mucosa or olfactory tissues were immunolocalized by immunohistochemistry. ENT1 and ENT2 expression was relatively high in nasal epithelia and olfactory bulb, which may explain the uptake of intranasally administered nucleoside derivatives observed by other investigators. OATP3 immunoreactivity was high in olfactory epithelium and olfactory nerve bundles, which suggests that substrates transported by OATP3 may be candidates for intranasal administration.
Footnotes
This work was supported in part by the National Institutes of Health National Institute of Diabetes and Digestive and Kidney Diseases [Grant DK068039]; and the University of Cincinnati Dean's Bridge Funding Program and Center for Environmental Genetics.
Article, publication date, and citation information can be found at http://dmd.aspetjournals.org.
doi:10.1124/dmd.110.034611.
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ABBREVIATIONS:
- CSF
- cerebral spinal fluid
- ENT
- equilibrative nucleoside transporters
- OB
- olfactory bulb
- OCT
- organic cation transporter
- OATP
- organic anion-transporting polypeptide
- MRP
- multidrug resistance protein
- BG
- Bowman's glands
- NLS
- nuclear localization sequence.
- Received May 20, 2010.
- Accepted July 21, 2010.
- Copyright © 2010 by The American Society for Pharmacology and Experimental Therapeutics
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