Koichi Takahashi (1), Hiroyuki Mizuno (1), Hiromitsu Ohno (1), Hirofumi
Kai (2), Yoichiro Isohama (2), Kazuo Takahama (2), Shigeru Nagaoka (3) and
Takeshi Miyata (2)
(1) Central Research Laboratories, SS Pharmaceutical Co., Ltd., 1143
Nanpeidai, Narita 286-8511, Japan
(2) Department of Pharmacological Sciences, Faculty of Pharmaceutical Sciences,
Kumamoto University, 5-1 Oe-honmachi, Kumamoto 862-0973, Japan
(3) Japan Research Institute of Sputum, 1-9-10, Chiyogaoka, Asao-ku, Kawasaki
215-0005, Japan
Abstract: We examined the effects of SS320A ((-)-(R)-2-amino-3-(3-hydroxypropylthio)propionic
acid), a new cysteine derivative, on the change in the number of goblet
cells induced by isoproterenol in rat tracheal epithelium. Four types of
goblet cells were characterized in tracheal epithelium according to their
size and staining affinity with Alcian blue (AB) / periodic acid Schiff
(PAS). When each rat was given a single daily injection of isoproterenol
(0.05 mg/kg, i.p.) for 14 days, a significant increase was observed in AB/PAS-positive
cells that were recognizable as goblet cells in tracheal epithelium. When
SS320A (10 - 100 mg/kg, p.o.) or propranolol (1 mg/kg, s.c.) was administered
before each injection of isoproterenol, the increase in the number of goblet
cells induced by isoproterenol was significantly inhibited. There was no
difference between male and female rats with regard to this inhibitory action.
On the other hand, ambroxol, bromhexine, L-cysteine ethyl ester and S-carboxymethylcysteine
(100 mg/kg, p.o., respectively), which are used as expectorants, had no
inhibitory effects on the isoproterenol-induced change in the number of
goblet cells. Four metabolites (M1 - M4) of SS320A in rats also failed to
inhibit the change induced by isoproterenol. These data suggest that SS320A
itself may have a beneficial effect against mucus hypersecretion in chronic
respiratory diseases.
Keywords: Cysteine derivative, Goblet cell, Isoproterenol, SS320A