Sodium Nitroprusside Enhances Absorption in the Rat Jejunum via the Transcellular Route

It was reported that nitric oxide (NO) donors increased the permeability of water-soluble compounds across intestinal membrane with neither loss of cell viability nor release of lactate dehydrogenase. Therefore, the detail mechanism of action of NO donors on the gastrointestinal membrane has yet to be clarified. We previously reported the possibility of the enhancing effect of the NO donor on the membrane permeability via transcellular route. The purpose of this study is to clarify the mechanism of the membrane permeation-enhancing effect via the transcellular route by sodium nitroprusside (SNP), which is one of the NO donors. The effect of SNP on membrane permeation was examined by the in vitro sac method using rat jejunum. SNP increased the membrane permeation of rhodamine 123 same as using N-acetyl-l-cysteine and dithiothreitol which removes unstirred water layer (UWL). Moreover, SNP increased the membrane permeation of antipyrine and beta-naphthol, which are transcellular markers. And it was also investigated the expression levels of mucins (MUCs) which are construction component of UWL and the slight change of MUCs expression by SNP was shown. It was suggested that the expression balance of MUCs is necessary to regulate transcellular permeation, and SNP may affect to UWL. This finding was considered useful for highly lipophilic drugs for which membrane permeation is restricted by the UWL.