Drug transporter expression and localization in rat nasal respiratory and olfactory mucosa and olfactory bulb

Mary Beth Genter, Mansi Krishan, Lisa M. Augustine, Nathan J Cherrington

Research output: Contribution to journalArticle

21 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1644-1647
Number of pages4
JournalDrug Metabolism and Disposition
Volume38
Issue number10
DOIs
StatePublished - Oct 1 2010

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Olfactory Mucosa
Respiratory Mucosa
Nasal Mucosa
Olfactory Bulb
Olfactory Nerve
Nasal Cavity
Pharmaceutical Preparations
Organic Cation Transporter 1
Equilibrative Nucleoside Transporter 1
Intranasal Administration
Multiple Drug Resistance
Xenobiotics
Nucleosides
Anions
Axons
Immunohistochemistry
Research Personnel
Technology
Kidney
Peptides

ASJC Scopus subject areas

  • Pharmacology
  • Pharmaceutical Science

Cite this

Drug transporter expression and localization in rat nasal respiratory and olfactory mucosa and olfactory bulb. / Genter, Mary Beth; Krishan, Mansi; Augustine, Lisa M.; Cherrington, Nathan J.

In: Drug Metabolism and Disposition, Vol. 38, No. 10, 01.10.2010, p. 1644-1647.

Research output: Contribution to journalArticle

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