Mucosal Protection by l-Arginine in the Upper Gastrointestinal Tract

Abstract

Arginine, a conditionally nonessential amino acid, is synthesized from citrulline by the sequential action of the cytosolic enzymes argininosuccinate synthetase and argininosuccinate lyase in the body and does not need to be obtained directly through the diet. However, since this biosynthetic pathway does not produce sufficient amounts of arginine, some needs to be consumed through the diet. This amino acid plays an important role in cell division, the healing of wounds, removal of ammonia from the body, immune function, and the regulation of cardiovascular aspects (Masumoto et al., Nutrition 27:1141–1145, 2011; Zhu et al., Innate Immun 19:242–252, 2013; Lorin et al., Mol Nutr Food Res 58:101–116, 2014). In addition, arginine is the precursor of nitric oxide (NO), which is synthesized from this amino acid by NO synthase, an enzyme involved in the modulation of various biological actions mainly through the activation of guanylyl cyclase under physiological conditions (Whittle, Physiology of the Gastrointestinal Tract, 1994). Several studies (Okabe et al., Arzneimittel-Forschung 26:534–537, 1997; Takeuchi et al., Jpn J Pharmacol 61:13–21, 1993; Tanaka et al., J Physiol Pharmacol 50:405–417, 1999; Ohno et al., J Pharmacol Exp Ther 310:821–827, 2004; Nagahama et al., Dig Dis Sci 51:303–309, 2006; Nagahama et al., Med Sci Monit 18:BR9–BR15, 2012) demonstrated that arginine exhibited protective effects against various lesion models in the gastrointestinal tract, including the esophagus. Although the mechanisms responsible have yet to be elucidated, the protective effects were reportedly related to processes dependent on or independent of NO (Tanaka et al., J Physiol Pharmacol 50:405–417, 1999; Ohno et al., J Pharmacol Exp Ther 310:821–827, 2004; Nagahama et al., Dig Dis Sci 51:303–309, 2006; Nagahama et al., Med Sci Monit 18:BR9–BR15, 2012).