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The NK 1 receptor and its participation in the synergistic enhancement of corneal epithelial migration by substance P and insulin‐like growth factor‐1
Author(s) -
Nakamura Masatsugu,
Ofuji Keiko,
Chikama Taiichiro,
Nishida Teruo
Publication year - 1997
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0700923
Subject(s) - insulin , receptor , insulin like growth factor , growth factor , insulin receptor , microbiology and biotechnology , endocrinology , chemistry , medicine , biology , insulin resistance
1 We have previously shown that substance P (SP) and insulin‐like growth factor‐1 (IGF‐1) act synergistically to enhance the migration of rabbit corneal epithelial cells in an organ culture model. The present study was designed to identify the epithelial cell SP receptor that participates in this synergistic effect. 2 Rabbit corneal blocks were incubated for 24 h, then the length of the path of epithelial migration was measured. Reagents tried in the TC‐199 culture medium, in the presence or absence of IGF‐1, were: SP, agonists of tachykinin receptors NK 1 ; NK 2 or NK 3 and antagonists of tachykinin receptors NK 1 or NK 2 . 3 The binding characteristics of SP receptors were examined in rabbit cultured corneal epithelial cells by binding assays with [ 125 I]‐SP in the presence or absence of excess unlabelled SP or ligands of NK l , NK 2 or NK 3 receptors. 4 As was demonstrated previously, SP and IGF‐1 stimulated epithelial migration when they were added to the culture medium together, but individually they had no effect. NK 1 agonists had the same synergistic effect with IGF‐1 as did SP, but the NK 2 and NK 3 agonists did not. Furthermore, the NK 1 antagonist abolished the synergistic effect of SP and IGF‐1, but the NK 2 antagonist had no effect. 5 SP bound specifically to rabbit cultured corneal epithelial cells. The binding affinity was 0.44 nM and there were 2.43 × 10 4 binding sites per cell. The NK 1 ligand competed, in a dose‐dependent fashion, with the binding of SP to corneal epithelial cells, but neither the NK 2 nor NK 3 ligand affected binding. 6 We conclude that the SP receptor in rabbit corneal epithelial cells is NK 1 and that this receptor participates in the synergistic enhancement of corneal epithelial migration by SP and IGF‐1. The precise mechanism(s) of this interaction requires more study. These findings imply that both neural and humoral factors are essential for the maintenance and healing of corneal epithelium.