Masakatsu Takahashi1,*, Hiroko Fukunaga1, Hiroshi
Kaneto2, Shin-ichi Fukudome3 and Masaaki Yoshikawa4
1Department of Pharmacoinformatics, School of Pharmaceutical
Sciences, Nagasaki University and 2Emeritus Professor, Nagasaki
University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan
3Food Research Laboratory, Nisshin Flour Milling Co., Ltd., Ohimachi,
Saitama 356-8511, Japan
4Research Institute for Food Scicence, Kyoto University, Uji,
Kyoto 611-0011, Japan
*Corresponding author.ﾊﾊPresent affiliation for correspondence: Department
of Analytical Research for Pharmacoinformatics, Graduate School of Pharmaceutical
Sciences, Nagasaki University, 1-14, Bunkyo-machi, Nagasaki 852-8521, Japan
FAX:+81-95-844-6774, E-mail: takahashi@net.nagasaki-u.ac.jp
Abstract: Central effects of gluten exorphinﾊ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ﾊA5 produced neither an antinociceptive effect nor an effect
on morphine analgesia. Intracerebroventricularly (i.c.v.) administered gluten
exorphinﾊA5 produced mild but significant antinociception in a dose-depepndent
manner, while not affecting the morphine analgesia. On the other hand, oral
gluten exorphinﾊA5 suppressed the endogenous pain-inhibitory system, i.e.,
antinociception induced by socio-psychological- (PSY-) stress (SIA) using
a communication box; intraperitoneal gluten exorphinﾊA5 abolished both footshock-
(FS-) stress-induced antinociception (SIA) and PSY-SIA; and i.c.v. gluten
exorphinﾊA5 suppressed FS-SIA, but rather potentiated PSY-SIA. This peptide
given by these routes was without effect on forced swim-SIA. In addition,
oral gluten exorphinﾊA5 tended to prolong the retention time on open arms
in the elevated plus-maze test. Finally, oral gluten exorphinﾊ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ﾊA5
has been found to produce various effects not only in the peripheral nervous
systems but also in the central nervous system.
Keywords: Gluten exorphinﾊA5, Stress-induced antinociception, Emotionality,
Learning/memory process, Morphine