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Voltage dependence of transepithelial guanidine permeation across Caco-2 epithelia allows determination of the paracellular flux component

Lookup NU author(s): Dr Georgina Carr, Iain Haslam, Professor Nicholas Simmons


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Purpose. The aim of this study was to investigate transepithelial ionic permeation via the paracellular pathway of human Caco-2 epithelial monolayers and its contribution to absorption of the base guanidine. Methods. Confluent monolayers of Caco-2 epithelial cells were mounted in Ussing chambers and the transepithelial conductance and electrical potential difference (p.d.) determined after NaCl dilution or medium Na substitution (bi-ionic conditions). Guanidine absorption (J a-b) was measured ± transepithelial potential gradients using bi-ionic p.d.'s. Results. Basal NaCl replacement with mannitol gives a transepithelial dilution p.d. of 28.0 ± 3.1 mV basal solution electropositive (P Cl/P Na = 0.34). Bi-ionic p.d.'s (basal replacements) indicate a cation selectivity of NH4+ > K+∼Cs+ > Na+ > Li+ > tetraethylammonium+ > N-methyl-d- glucamine+∼choline+. Transepithelial conductances show good correspondence with bi-ionic potential data. Guanidine J a-b was markedly sensitive to imposed transepithelial potential difference. The ratio of guanidine to mannitol permeability (measured simultaneously) increased from 3.6 in the absence of an imposed p.d. to 13.8 (basolateral negative p.d.). Conclusions. Hydrated monovalent ions preferentially permeate the paracellular pathway (Eisenman sequence 2 or 3). Guanidine may access the paracellular pathway because absorptive flux is sensitive to the transepithelial potential difference. An alternative method to assess paracellular-mediated flux of charged organic molecules is suggested. © 2006 Springer Science + Business Media, Inc.

Publication metadata

Author(s): Carr G, Haslam IS, Simmons NL

Publication type: Article

Publication status: Published

Journal: Pharmaceutical Research

Year: 2006

Volume: 23

Issue: 3

Pages: 540-548

ISSN (print): 0724-8741

ISSN (electronic): 1573-904X

Publisher: Springer New York LLC


DOI: 10.1007/s11095-006-9568-2


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