Role of dopamine transporter (DAT) in dopamine transport across the nasal mucosa

Behavioral Actions of Intranasal Application of Dopamine: Effects on Forced Swimming, Elevated Plus-Maze and Open Field Parameters

“…While systemic circulation of DA into the brain seems unlikely, due to its hydrophilic properties that prevent penetration through the blood-brain barrier, several pathways have been suggested for the transport of substance from the nose to the brain, such as the olfactory epithelial pathway, systemic circulation from the nasal mucosa, and the olfactory nerve pathway [1] . Recently, it was demonstrated that portions of the nasal mucosa are innervated by olfactory neurons expressing the dopamine transporter (DAT), which is responsible for the uptake of DA [15] , providing a possible mechanism by which exogenous DA could have entered the brain. Assessing the exact transport pathway of intra-nasal DA remains to be examined in future research.…”

“…With respect to this, Dahlin et al [13,14] compared intra-nasal to intravenous DA injection and reported an enhanced DA bioavailability in the brain upon intra-nasal administration of DA in mice and rats. Furthermore, Chemuturi et al [15] demonstrated that portions of the nasal mucosa are innervated by olfactory neurons expressing dopamine transporter (DAT), which may be responsible for the uptake of DA within the central nervous system. Several pathways for the transport of substances from the nose to the brain have been suggested to circumvent the BBB, such as the slow olfactory nerve pathway (axonal transport pathway) or the fast olfactory epithelial pathway, where substance absorption takes place either by transcellular or paracellular mechanisms across the olfactory sustentacular epithelial cells [for review, see 1,16 ].…”

Intranasal delivery of dopamine to the striatum using glycol chitosan/sulfobutylether-β-cyclodextrin based nanoparticles

“…The treatment of PD by exogenous administration of DA is hampered by its inability to overcome the blood brain barrier (BBB) [5]. As well documented, the physiological role of the BBB is to maintain brain homeostasis allowing the transport of nutrients and the exclusion of toxic substances from the brain.…”

“…The DA inability to overcome the BBB is mainly attributed to its unfavorable physicochemical features as high hydrogen bonding potential and complete ionization at physiological pH and, moreover, it is extensively metabolized by liver when orally administered [5,8]. Instead of the oral and intravenous route, the intranasal drug administration is receiving great consideration as a promising pharmacokinetic approach for the PD treatment.…”

“…Thus, DA may be transported into the brain exploiting the ''Large neutral Amino acid'' Transporter (LAT) carrier which is able to transport not only L-Dopa but also other aminoacid-related compounds as DA [24]. In addition, Chemuturi and colleagues described enhanced CNS uptake of DA following intranasal administration due to the presence of DA Transporter (DAT) and Organic Cation Transporter-2 (OCT-2) in the nasal mucosa [5,25]. Moreover, DA is metabolized in limited extent by the nasal mucosa to its main metabolite dihydroxyphenylacetic acid (DOPAC) [26].…”