INHIBITORY ACTION OF POLYCATIONIC PEPTIDES ON HORMONAL REGULATION OF ADENYLYL CYCLASE OF THE CILIATE
DILEPTUS ANSER
A. O. Shpakov,1 K. V. Derkach,1 I. A. Gurjanov,2
Z. I. Uspenskaya,3 L. A. Kuznetsova,1
S. A. Plesneva,1 G. P. Vlasov,1 M. N. Pertseva 1
1 I. M. Sechcnov Institute of Evolutionary Physiology and Biochemistry, RAS,
2 Institute of Macromolccular Compounds, RAS, and
3 Institute of Cytology, RAS, St. Petersburg, Russia;
e-mail: alex_shpakov@list.ru
To analyse molecular mechanisms of regulatory action of different hormones on the activity of the adenylyl
cyclase signaling system (ACS) of the ciliate Dileptus anser, we studied the influence on this process of six synthetic
polycationic peptides and peptides, corresponding to C-terminal regions of mammalian G-protein 385-394 αs- and
346-355 αi2-subunits. As we reported earlier, these peptides block hormonal signal transduction in tissues of
the higher eukaryotes. Now it has been found that both polycationic peptides, containing hydrophobic Ñ10-radicals, and
branched peptides decrease regulatory effects of peptide hormones (insulin, relaxin) and biogenic amines (serotonin, adrenaline)
on adenylyl cyclase (AC) activity and GTP-binding. In regard to the following peptides
Cys-εAhx-Trp-Lys-Lys(C10)-Lys2-Lys(C10)-Lys3-Lys(C10)-Tyr-Lys-
Lys(C10)-Lys-Lys-amide and [(Gly-Arg-Gly-Asp-Ser-Gly-Arg-Lys-Lys-Arg-Arg-Gln-Arg-Arg-Arg-Arg-Pro-Pro-Gln)2-
Lys-sAhx-Cys]2 (εAhx - ε-aminocaproyl, Ñ10 - caprinoyl group) their dose-dependent inhibitory
action is shown. In cell culture of D. anser with a lower basal AC activity, both hydrophobic and branched peptides
stimulated AC and GTP-binding without hormones. The data give evidence that these peptides can activate ACS of ciliates in a
receptor-independent manner. No influence of peptides 385-394 αs and 346-355 αi2 on hormonal
signal transduction in D. anser was observed, due, presumably, to some structural differences of G-proteins of the lower
and higher eukaryotes. A conclusion was made about an important role of polycationic regions for functional coupling of
hormone-activated receptor and G-proteins in the ciliate D. anser.
Key words: adenylyl cyclase, heterotrimeric G-protein, GTP-binding, insulin, ciliate, Dileptus anser,
polycationic peptide, relaxin, serotonin
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