Stress-Protective Effect of the Synthetic ACTH-Like Peptide Leucocorticotropin

V. I. Vaninaa, Yu. A. Kovalitskayaa, A. A. Kolobovb, E. A. Kampe-Nemmb, Yu. A. Zolotarevc, V. V. Yurovskiid, V. M. Lipkina, and E. V. Navolotskayaa,#

# Phone: (27) 73-6668; fax: (27) 33-0527; e-mail: navolots@fibkh.serpukhov.su
a ShemyakinOvchinnikov Institute of Bioorganic Chemistry (Pushchino Branch), Russian Academy of Sciences, pr. Nauki 6, Pushchino, Moscow oblast, 142292 Russia
b State Research Center Institute of Highly Pure Biopreparations, Federal Agency for Healthcare and Social Development, Pudozhskaya ul. 7, St. Petersburg, 197110 Russia
c Institute of Molecular Genetics, Russian Academy of Sciences, pl. Kurchatova 2, Moscow, 123182 Russia
d Department of Medicine, University of Maryland, Baltimore, MD, 21201 USA

Received November 14, 2005; in final form, December 12, 2005

Abstract: We found that the tritium-labeled synthetic ACTH-like octapeptide leucocorticotropin corresponding to the 81--88 sequence of the precursor of human interleukin-1α ([3H]GKVLKKRR) is bound by the ACTH receptor of rat adrenal cortex with a high affinity and specificity (Kd 2.2 ± 0.1 nM). This peptide was shown to exert no effect on the adenylate cyclase activity of the membranes of rat adrenal cortex in the concentration range from 1 to 1000 nM. Leucocorticotropin administration three times at doses of 10–20 μg/animal did not change the level of hydroxycorticosteroids (11-HOCS) in the rat adrenal glands in the absence of temperature action. At the same time, the peptide abolishes (at a dose of 20 μg/animal, three times) or significantly decreases (at a dose of 10 μg/animal, three times) the dramatic increase in the 11-HOCS content in the adrenal glands occurring in the case of cold or heat shock. Thus, leucocorticotropin normalizes the 11-HOCS level in the rat adrenal cortex during stress. The stress-protective effect of the peptide is mediated through the ACTH receptor.

Key words: adrenal cortex, adrenocorticotropic hormone, interleukin-1, peptides, receptors

Russian Journal of Bioorganic Chemistry 2006, 32 (5):429-435