RT Journal Article
SR Electronic
T1 Drug Transporter Expression and Localization in Rat Nasal Respiratory and Olfactory Mucosa and Olfactory Bulb
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 1644
OP 1647
DO 10.1124/dmd.110.034611
VO 38
IS 10
A1 Genter, Mary Beth
A1 Krishan, Mansi
A1 Augustine, Lisa M.
A1 Cherrington, Nathan J.
YR 2010
UL http://dmd.aspetjournals.org/content/38/10/1644.abstract
AB 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.