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

Carr, Georgina, Haslam, Iain S. and Simmons, Nicholas L. (2006) Voltage dependence of transepithelial guanidine permeation across Caco-2 epithelia allows determination of the paracellular flux component. Pharmaceutical Research, 23 (3). pp. 540-548. ISSN 0724-8741

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Abstract

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 (Ja-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 (PCl/PNa = 0.34). Bi-ionic p.d.'s (basal replacements) indicate a cation selectivity of NH4+ > K+ approximately Cs+ > Na+ > Li+ > tetraethylammonium+ > N-methyl-D: -glucamine+ approximately choline+. Transepithelial conductances show good correspondence with bi-ionic potential data. Guanidine Ja-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.

Item Type:	Article
Subjects:	Q Science > QH Natural history > QH301 Biology R Medicine > RM Therapeutics. Pharmacology
Schools:	School of Applied Sciences School of Applied Sciences > Biomolecular Sciences Research Centre
Depositing User:	Iain Haslam
Date Deposited:	11 Nov 2015 10:02
Last Modified:	11 Nov 2015 10:26
URI:	http://eprints.hud.ac.uk/id/eprint/26431

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