ORGANIC ANION TRANSPORTERS - Drug Transporters: Molecular Characterization and Role in Drug Disposition - page 58

Phase Contrast Fluorescence Merge

(a) (b) (c)

(d) (e) (f)

(g) (h) (i)

(j) (k) (l)

FIGURE 4.4. Confocal microscopic images showing fluorescein accumulation in induced
metanephric mesenchyme (MM) due to expression of organic anion transporters. Control;
( a - i ) or presence of 2 mM probenecid (probenecid; j - l ). ( a , d , g , j ) Phase-contrast photomi-
crographs of the induced epithelial tubular structures. ( b , e , h , k ) Corresponding fluorescence
photomicrograph of the tissue shown in the preceding panel. ( c , f , i , l ) Merged image of the two
preceding photomicrographs, indicating the accumulation of fluorescein in the induced MM.
( a - c ) Low-magnification examination of a group of tubular structures in the induced mes-
enchyme in the absence of probenecid; bar = 100 μ M. ( d - f ) High-magnification examination
of tubular structures in the mesenchyme induced in the absence of probenecid; bar = 20 μ M.
( g - i ) Higher-magnification examination of a tubular structure in the induced mesenchyme in
the absence of probenecid; bar = 20 μ M. Note the accumulation of fluorescein, to a concentra-
tion greater than the medium, in what appears to be a fluid-filled space (presumptive lumen).
( j - l ) Low-magnification examination of a group of tubular structures in the mesenchyme in-
duced in the presence of 2 mM probenecid; bar = 100 μ M. Note the absence of concentrative
fluorescein accumulation. (From ref. 29.) ( See insert for color representation of figure. )

interconnecting loops in OAT1, one between TMD 1/2, and another between TMD
6/7 13 , 33 − 35 (Figure 4.5). The first large loop is extracellular and contains multiple
consensus N-glycosylation sites. The role of these sites in the regulation of transport
function has not been determined, although glycosylation of OAT1 was shown to be
required for protein trafficking to the membrane. 36 The second large loop is intracellu-
lar and contains several canonical protein kinase C (PKC) phosphorylation sites. 35 , 37