caa a22 4500 477126049 CHVBK 20180405111650.0 cr unu---uuuuu 170330e19970901xx s 000 0 eng 10.1023/A:1012123411343 doi (NATIONALLICENCE)springer-10.1023/A:1012123411343 Polar Solute Transport Across the Pigmented Rabbit Conjunctiva: Size Dependence and the Influence of 8-Bromo Cyclic Adenosine Monophosphate [Elektronische Daten] [Yoshihide Horibe, Ken-ichi Hosoya, Kwang-Jin Kim, Taro Ogiso, Vincent Lee] Purpose. To characterize the conjunctival permeability to polar solutes ranging from 182 to 167,000 daltons in molecular weight (m.w.). Methods. Solute transport across the excised pigmented rabbit conjunctiva with a baseline transepithelial electrical resistance (TEER) of 1,285 ± 46 ohm·cm2 was evaluated in the modified Ussing chamber under open-circuit conditions. The model solutes were mannitol (m.w. 182), 6-carboxyfluorescein (m.w. 376), and fluorescein isothiocyanate-labeled dextrans (FD4, m.w. 4,400—FD150, m.w. 167,000). Results. For a given solute, the apparent permeability coefficient (Papp) was independent of solute concentration and direction of transport. As expected, the Papp decreased with solute size, from 27.7 × 10−8 cm/sec for mannitol to 0.31 × 10−8 cm/sec for FD150. When the experimental temperature was lowered from 37°C to 4°C, Papp decreased by ~50% for FD4 through FD40 and by >80% for both FD70 and FD150. Equivalent pore analysis, assuming restricted solute diffusion via cylindrical, water-filled pores across the isolated tissue, revealed a radius of 5.5 nm at a pore density of 1.9 × 108 pores per cm2. The addition of 1 mM 8-bromo cyclic adenosine monophosphate (8-BrcAMP), known to stimulate Cl− secretion and decrease TEER, to the mucosal side of the conjunctiva increased the transport of mannitol, FD4, and FD40 by 28%, while not affecting FD150 transport. Conclusions. Our findings suggest that polar solutes up to FD40 traverse the conjunctival epithelial barrier primarily by restricted diffusion through equivalent pores of 5.5 nm radius and that solute movement is affected by reduction of TEER. On the other hand, polar solutes of the FD70 or larger may cross the barrier primarily via non-diffusional pathways such as non-specific endocytosis. Plenum Publishing Corporation, 1997 conjunctival epithelium nationallicence conjunctival drug delivery nationallicence cyclic adenosine monophosphate nationallicence equivalent pores nationallicence Horibe Yoshihide Department of Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 90033, Los Angeles, California aut Hosoya Ken-ichi Department of Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 90033, Los Angeles, California aut Kim Kwang-Jin Will Rogers Institute Pulmonary Research Center, University of Southern California, 90033, Los Angeles, California aut Ogiso Taro Faculty of Pharmaceutical Sciences, Kinki University 3-4-1 Kowakae, Higashi-, 577, Osaka, Japan aut Lee Vincent Department of Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 90033, Los Angeles, California aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/9(1997-09-01), 1246-1251 0724-8741 14:9<1246 1997 14 11095 https://doi.org/10.1023/A:1012123411343 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012123411343 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Horibe Yoshihide Department of Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 90033, Los Angeles, California aut NATIONALLICENCE 700 1- Hosoya Ken-ichi Department of Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 90033, Los Angeles, California aut NATIONALLICENCE 700 1- Kim Kwang-Jin Will Rogers Institute Pulmonary Research Center, University of Southern California, 90033, Los Angeles, California aut NATIONALLICENCE 700 1- Ogiso Taro Faculty of Pharmaceutical Sciences, Kinki University 3-4-1 Kowakae, Higashi-, 577, Osaka, Japan aut NATIONALLICENCE 700 1- Lee Vincent Department of Pharmaceutical Sciences, School of Pharmacy, University of Southern California, 90033, Los Angeles, California aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/9(1997-09-01), 1246-1251 0724-8741 14:9<1246 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer