title: [Comparative study of molecular mechanisms of natural and synthetic polycationic peptides action on the activity of the adenylyl cyclase signaling system].
abstract: The molecular mechanisms of action of natural and synthetic polycationic peptides, forming amphiphilic helices, on the heterotrimeric G-proteins and enzyme adenylyl cyclase (AC), components of hormone-sensitive AC system, were studied. It is shown that synthetic peptides C-epsilonAhx-WKK(C10)-KKK(C10)-KKKK(C10)-YKK(C10)-KK (peptide I) and (GRGDSGRKKRRQRRRPPQ)2-K-epsilonAhx-C(Acm)(peptide II) in dose-dependent manner stimulate the basal AC activity, inhibit forskolin-stimulated AC activity and decrease both stimulating and inhibiting AC effects of the hormones in the tissues (brain striatum, heart muscle) of rat and in smooth muscles of the mollusc Anodonta cygnea. AC effects of these peptides are decreased after membrane treatment by cholera and pertussis toxins and are inhibited in the presence of the peptides, corresponding to C-terminal regions 385-394 alphas- and 346-355 alphai2-subunits of G-proteins. These data give evidence that the peptides I and II act on the signaling pathways which are realized through Gs- and Gi-proteins. At the same time, natural polycationic peptide mastoparan acts on AC system through Gi-proteins and blocks hormonal signals mediated via Gi-proteins only. Consequently, the action of mastoparan on G-proteins is selective and differs from the action of the synthetic peptides. It is also shown that peptide II, with branched structure, directly interacts not only with G-proteins (less effective in comparison with peptide I with hydrophobic radicals and mastoparan), but also with enzyme AC, the catalytic component of AC system. On the basis of data obtained the following conclusions were made: 1) the formation of amphiphilic helices is not enough for selective activation of G-protein by polycationic peptides, and 2) the primary structure of the peptides, the distribution of positive charged amino acids and hydrophobic radicals in them are very important for selective interaction between polycationic peptides and G-proteins.
authors.forename: A O
authors.initials: AO
authors.lastname: Shpakov
authors.forename: I A
authors.initials: IA
authors.lastname: Gur'ianov
authors.forename: L A
authors.initials: LA
authors.lastname: Kuznetsova
authors.forename: S A
authors.initials: SA
authors.lastname: Plesneva
authors.forename: E T
authors.initials: ET
authors.lastname: Zakharova
authors.forename: G P
authors.initials: GP
authors.lastname: Vlasov
authors.forename: M N
authors.initials: MN
authors.lastname: Pertseva
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D049877:Anodonta; D001427:Bacterial Toxins / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000201:enzymology; D005576:Colforsin / Q000494:pharmacology; D003342:Corpus Striatum / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006728:Hormones / Q000494:pharmacology; D036341:Intercellular Signaling Peptides and Proteins; D009130:Muscle, Smooth / Q000187:drug effects / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology*; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects*; D013574:Synaptosomes / Q000187:drug effects / Q000201:enzymology; D014862:Wasp Venoms / Q000494:pharmacology*
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D001427:Bacterial Toxins; D006728:Hormones; D036341:Intercellular Signaling Peptides and Proteins; D010455:Peptides; D014862:Wasp Venoms; D005576:Colforsin; C037500:mastoparan; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases