Behavioral and Pharmacological Studies on Gluten Exorphin A5, a Newly Isolated Bioactive Food Protein Fragment, in Mice.

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  • Takahashi Masakatsu
    Department of Pharmacoinformatics, School of Pharmaceutical Sciences, Nagasaki University 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan
  • Fukunaga Hiroko
    Department of Pharmacoinformatics, School of Pharmaceutical Sciences, Nagasaki University 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan
  • Kaneto Hiroshi
    Emeritus Professor, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan
  • Fukudome Shin-ichi
    Food Research Laboratory, Nisshin Flour Milling Co., Ltd., Ohimachi, Saitama 356-8511, Japan
  • Yoshikawa Masaaki
    Research Institute for Food Science, Kyoto University, Uji, Kyoto 611-0011, Japan

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Abstract

Central effects of gluten exorphin A5 (Gly-Tyr-Tyr-Pro-Thr), a fragment from wheat gluten, were studied on the pain-inhibitory system, emotionality and learning/memory processes in mice. Orally administered gluten exorphin A5 produced neither an antinociceptive effect nor an effect on morphine analgesia. Intracerebroventricularly (i.c.v.) administered gluten exorphin A5 produced mild but significant antinociception in a dose-dependent manner, while not affecting the morphine analgesia. On the other hand, oral gluten exorphin A5 suppressed the endogenous pain-inhibitory system, i.e., antinociception induced by socio-psychological- (PSY-) stress (SIA) using a communication box; intraperitoneal gluten exorphin A5 abolished both footshock- (FS-) stress-induced antinociception (SIA) and PSY-SIA; and i.c.v. gluten exorphin A5 suppressed FS-SIA, but rather potentiated PSY-SIA. This peptide given by these routes was withuot effect on forced swim-SIA. In addition, oral gluten exorphin A5 tended to prolong the retention time on open arms in the elevated plus-maze test. Finally, oral gluten exorphin A5 when given during the post-training period of learning/memory processes significantly increased the latency into the dark compartment in the one-trail step-though type passive avoidance test, indicating that the peptide also facilitates the acquire/consolidation process of learning/memory. Thus, gluten exorphin A5 has been found to produce various effects no only in the peripheral nervous systems but also in the central nervous system.

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