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:
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 1020 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