Abstract
We examined the enhancing action of sodiumcaprate and palmitoylcarnitine on the permeability offluorescein isothiocyanate dextran 4000 as aparacellular permeant compound in isolated rat and humancolon samples using the Ussing-type chamber method.In the absence of an enhancer, the permeation clearanceof fluorescein isothiocyanate dextran 4000 was notsignificantly different in the rat and human colons, but the electric membrane resistance wassmaller in the rat colon than in the human colon. Sodiumcaprate and palmitoylcarnitine increased permeationclearance and decreased electric membrane resistance in both types of colonic membrane, showing thatthe rat colon can be used as a model of the human colonfor studies of enhancer effects. A calmodulin antagonistsignificantly inhibited the action of sodium caprate in both colonic membranes. However, ittended to promote the effects of palmitoylcarnitine onpermeation clearance and electric membrane resistance.These results suggest that sodium caprate induces the contraction of the perijunctionalactomyosin ring to widen the tight junction and that themechanism of palmitoylcarnitine is different from thatof sodium caprate in the human colon, as reportedpreviously for Caco-2 cell monolayers.
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REFERENCES
Powell DW: Barrier function of epithelia. Am J Physiol 241:G275-G288, 1981
Tomita M, Shiga M, Hayashi M, Awazu S: Enhancement of colonic drug absorption by the paracellular permeation route. Pharm Res 5:341-346, 1988
Sawada T, Ogawa T, Tomita M, Hayashi M, Awazu S: Role of parace llular pathway in nonelectrolyte permeation across rat colon epithelium enhanced by sodium caprate and sodium capryrate. Pharm Res 8:1365-1371, 1991
Anderberg EK, Lindmark T, Artursson P: Sodium caprate elicits dilatations in human intestinal tight junction and enhance s drug absorption by the paracellular route. Pharm Res 10:857-864, 1993
Kajii H, Horie T, Hayashi M, Awazu S: Fluorescence study of the membrane perturbing action of sodium caprylate as related to promotion of drug absorption. J Pharm Sci 77:390-392, 1988
Tomita M, Hayashi M, Awazu S: Absorption-enhancing mechanism of EDTA, caprate, and decanoylcarni tine in Caco-2 cells. J Pharm Sci 85:608-611, 1996
Fix JA, Engle K, Porter PA, Leppert PS, Selk SJ, Gardner CR, Alexander J: Acylcarnitine: Drug absorption-enhancing agents in the gastrointestinal tract. Am J Physiol 251:G332-G340, 1986
LeCluyse EL, Appel LE, Sutton SC: Relationship between drug absorption enhancing activity and membrane perturbation effects of acylcarnitine. Pharm Res 8:84-87, 1991
Sutton SC, Forbes AE, Cargill R, Hochman JH, LeCluyse EL: Stimulations in vitromeasureme nt of intestinal tissue permeability and transepithelial electrical resistance (TEER) using Sweetana-Grass diffusion cells. Pharm Res 9:316-319, 1992
LeCluyse EL, Sutton SC, Fix JA: In vitroeffects of long-chain acylcarnitine on the permeability, transepithelial ele ctrical resistance and morphology of rat colonic mucosa. J Pharmacol Exp Ther 265:955-962, 1992
Hochman JH, Fix JA, LeCluyse EL: In vitroand in vivoanalysis of the mechanism of absorption enhancement by palmitoylcarnitine. J Pharmacol Exp Ther 269:813-822, 1994
Madara JL, Pappenheimer JR: Structural basis for physiological regulation of parace llular pathways in intestinal epithelia. J Membr Biol 100:149-164, 1987
Yamashita S, Saitoh H, Nakanishi K, Masada M, Nadai T, Kimura T: Effects of diclofenac sodium and disodium ethylenediaminetetraace tate on electrical parameters of the mucosal membrane and their relation to the permeability enhancing effects in the rat jejunum. J Pharm Pharmacol 39:621-622, 1987
Kanamori M, Naka M, Asano M, Hidaka H: Effects of N-(6-aminohexyl)-5-chloro-1-naphthalenasulfonamide and other calmodulin antagonists (calmodulin interaction agents) on calcium-induced contraction of rabbit aortic strips. J Pharmacol Exp Ther 217:494-499, 1981
Kawamoto S, Hidaka H: 1-( 5-I soquinol ine sulfonyl)-2-me thylpiperazine (H7) is a sele ctive inhibitor of protein kinase C in rabbit platelets. Biochim Biophys Res Commun 125:258- 264, 1984
Tomita M, Hayashi M, Awazu S: Absorption-enhancing me chanism of sodium caprate and decanoylcarni tine in Caco-2 cells. J Pharmacol Exp Ther 272:739-743, 1995
Tomita M, Hayashi M, Awazu S: Absorption-enhancing me chanism of EDTA, caprate and decanoylcarn itine in Caco-2 cells. J Pharm Sci 85:608-611, 1996
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Shimazaki, T., Tomita, M., Sadahiro, S. et al. Absorption-Enhancing Effects of Sodium Caprate and Palmitoyl Carnitine in Rat and Human Colons. Dig Dis Sci 43, 641–645 (1998). https://doi.org/10.1023/A:1018835829643
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DOI: https://doi.org/10.1023/A:1018835829643