Ion and Organic Solute Transport

The conjunctiva is a tight epithelium with an electrical resistance of 1.4 kohm-cm2 (Kompella et al., 1993) (Fig. 5). The potential difference of the conjunctiva is lumen-negative like the cornea, suggesting a net secretion of anions and/or a net absorption of cations.

Figure 5 Putative ion and solute transport processes in the mammalian conjunc-tival epithelium.

The conjunctiva actively secretes CP (Kompella et al., 1993), and about 80% of the conjunctival active ion transport is accounted for by CP secretion through apically localized channels. CP enters the basolateral side via Na + / K + /CP cotransport energized by the basolateral Na + /K + -ATPase. Conjunctiva secretes fluid secondary to active CP secretion (Shiue et al., 2000). Active Na+ absorption can counter this fluid secretion. Net fluid secretion rate across the conjunctiva is altered by pharmacological agents known to affect active CP secretion or Na+ absorption (Shiue et al., 2000).

Evidence exists for the presence of ion-dependent solute transport processes such as Na + -glucose, Na + -amino acid, and Na + -nucleoside transporters in the conjunctival epithelium (Kompella et al., 1995; Hosoya et al., 1996; Hosoya et al., 1998b). After bathing conjunctiva in a glucose-free glutathione bicarbonate Ringer (GBR) solution, mucosal addition of D-glucose elevated short-circuit current (Isc) by a maximum of 20% in a dose-dependent manner. Phlorizin, a specific inhibitor of Na + -glucose cotransporter, reduced the Isc in a dose-dependent manner, suggesting the possible apical localization of Na+-glucose cotransporter in the pigmented rabbit conjunctiva (Hosoya et al., 1996). Similarly, mucosal addition of glycine, L-arginine, D-arginine, and L-glutamic acid have increased Isc in the presence but not in the absence of sodium in the medium, suggesting the possible existence of Na + -amino acid cotransporters on the apical side of the conjunctiva (Kompella et al., 1995). Furthermore, B0, + , a sodium-dependent transporter of neutral (L-Glu) and basic amino acids (L-Arg, L-Lys, and NG-nitro-L-arginine) is present in the conjunctiva (Hosoya et al., 1998a).

Uridine, a nucleoside, is transported preferentially from the mucosal to serosal direction in a temperature- and phlorizin-sensitive manner across the conjunctiva (Hosoya et al., 1998b). At constant Na+ concentration (141 mM) on mucosal side, uridine increased Isc in a dose-dependent fashion. At constant uridine concentration (10 mM), increasing Na+ concentration increased Isc with a Hill coefficient of 1.1, suggesting that there is a 1:1 coupling in the transport of Na+ and uridine. Na + -dependent uridine transport was inhibited by 10 mM adenosine, guanosine, and inosine, but not by thymidine, suggesting that the transport process may be mainly selective for purine nucleosides.

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