T. Yamaki et al., ACTH-releasing activity and cAMP accumulation of rat urocortin-related peptides in pituitary corticotropic cells, BIOMED RES, 20(6), 1999, pp. 339-344
To investigate the structure-function relationship of urocortin (Ucn), ten
Ucn-related peptides lacking C- or N-terminal amino acid residues were prep
ared by solid phase technology. ACTH release and cAMP accumulation induced
by these synthetic peptides were examined in the mouse anterior pituitary t
umor cell line, AtT-20. Among ten Ucn-related peptides tested, Ucn(3-40) wa
s found to be nearly equipotent to Ucn in the activities inducing ACTH rele
ase and cAMP accumulation, suggesting that two N-terminal amino acids may n
ot be crucial for these actions of Ucn. On the other hand, Ucn(23-40) and U
cn(28-40) caused extremely low ACTH release. ACTH release was extremely low
when AtT-20 was stimulated by synthetic peptides lacking six amino acids i
n the C-terminal region of Ucn, such as Ucn(1-34), Ucn(3-34), Ucn(5-34), an
d Ucn(8-34); and by synthetic peptides lacking C-terminal region of Ucn, Uc
n(23-34) and Ucn(1-18). These results indicate that the C-terminal hexapept
ide region of Ucn is of extreme importance for the activity of Ucn to cause
ACTH release. Little, if any, cAMP accumulation was observed in the presen
ce of Ucn(5-34), Ucn(8-34), Ucn(23-34) or Ucn(1-18), supporting clearly tha
t the C-terminal 35-40 sequence of Ucn may be responsible for CRF/Ucn recep
tor binding.