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Structural and compositional determinants of cortistatin activity
Author(s) -
Criado José R.,
Li Haitao,
Jiang Xiaohui,
Spina Mariarosa,
HuitrónReséndiz Salvador,
Liapakis George,
Calbet Marta,
Siehler Sandra,
Henriksen Steven J.,
Koob George,
Hoyer Daniel,
Sutcliffe J. Gregor,
Goodman Murray,
de Lecea Luis
Publication year - 1999
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/(sici)1097-4547(19990615)56:6<611::aid-jnr7>3.0.co;2-g
Subject(s) - hippocampal formation , somatostatin , chemistry , neuropeptide , receptor , biological activity , neuroscience , biochemistry , biophysics , biology , in vitro
Cortistatin‐14 (CST‐14) is a putative novel neuropeptide that shares 11 of its 14 residues with somatostatin‐14 (SRIF‐14), yet its effects on sleep physiology, locomotor behavior and hippocampal function are different from those of somatostatin. We studied the structural basis for cortistatin's distinct biological activities. As with SRIF‐14, CST‐14 does not show any preferred conformation in solution, as determined by circular dichroism and nuclear magnetic resonance. Synthetic cortistatin analogs were designed and synthesized based on the cyclic structure of octreotide. Biological assays were carried out to determine their binding affinities to five somatostatin receptors (sst1‐5) and their ability to produce changes in locomotor activity and to modulate hippocampal physiology and sleep. The results show that the compound with N‐terminal proline and C‐terminal lysine amide exhibits cortistatin‐like biological activities, including reduction of population spike amplitudes in the hippocampal CA1 region, decrease in locomotor activity and enhancement of slow‐wave sleep 2. These findings suggest that both proline and lysine are necessary for cortistatin binding to its specific receptor. J. Neurosci. Res. 56:611–619, 1999. © 1999 Wiley‐Liss, Inc.