title: [The receptor of serpentine type and the heterotrimeric G protein as targets of action of the polylysine dendrimers].
abstract: The molecular mechanisms of action of the polycationic peptides--polylysine homo- and heterodendrimers on functional activity of biogenic amines- and peptide hormones-sensitive adenylyl; cyclase signaling system (AC system) in the myocardium and the brain of rats were studied. These peptides are expected to be used as highly effective polymer carries for biologically active substances. The polylysine homodendrimers of the third [(NH2)16(Lys)8(Lys)4(Lys)2Lys-Ala-NH2] (I), fourth [(NH2)32(Lys)16(Lys)8(Lys)4(Lys)2Lys-Ala-NH2 (II) and fifth [(NH2)64(Lys)32(Lys)16(Lys)8(Lys)4(Lys)2Lys-Ala-NH2] (III) generations and the polylysine homodendrimers of fifth generation--[(NH2)64(Lys-Glu)32(Lys-Glu)16(Lys-Glu)8(Lys-Glu)4(Lys-Glu)2Lys-Ala-Ala-Lys (ClAc)-Ala-NH2] (IV), [(NH2)64(Lys-Ala)32(Lys-Ala)16(Lys-Ala)8(Lys-Ala)4(Lys-Ala)2Lys-Ala-Lys(ClAc)-Ala-Ala-NH2] (V) and [(NH2)64(Lys-Gly-Gly)32(Lys-Gly-Gly)16(Lys-Gly-Gly)8(Lys-Gly-Gly)4(Lys-Gly-Gly)2 Lys-Gly-Gly-Lys(ClAc)-Ala-Ala-NH2] (VI) showed receptor-independent mechanism of heterotrimeric G-proteins activity, preferably of inhibitory type, interacting with C-terminal regions of their alpha-subunits. The homodendrimers II and III and heterodendrimer V are more effective G-protein activators. The polylysine dendrimers disturbed the functional coupling of the receptors of biogenic amines and peptides hormones with Gi-proteins and, in a lesser extent, Gs-proteins. This is illustrated by the decrease in regulatory effects of the hormones on AX activity and G-protein GTP binding and by the decrease in receptor affinity to agonists in the presence of the polylysine dendrimers, as result of receptor--G-proteins complex dissociation. It was shown also that the molecular mechanisms and the selectivity of the action on the G-proteins of the polylysine dendrimers were similar to those of mastoparan and melittin, natural toxins of insect venom.
authors.forename: A O
authors.initials: AO
authors.lastname: Shpakov
authors.forename: I A
authors.initials: IA
authors.lastname: Gur'ianov
authors.forename: N V
authors.initials: NV
authors.lastname: Baianova
authors.forename: G P
authors.initials: GP
authors.lastname: Vlasov
mesh_terms: D000262:Adenylyl Cyclases / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000648:ultrastructure; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D050091:Dendrimers / Q000138:chemical synthesis / Q000494:pharmacology*; D020962:Heterotrimeric GTP-Binding Proteins / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D009206:Myocardium / Q000378:metabolism / Q000648:ultrastructure; D010455:Peptides / Q000494:pharmacology; D011107:Polylysine / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D017982:Receptors, Biogenic Amine / Q000819:agonists / Q000037:antagonists & inhibitors / Q000187:drug effects*; D046948:Secologanin Tryptamine Alkaloids / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D050091:Dendrimers; D010455:Peptides; D017982:Receptors, Biogenic Amine; D046948:Secologanin Tryptamine Alkaloids; D011107:Polylysine; C009244:serpentine (alkaloid); D020962:Heterotrimeric GTP-Binding Proteins; D000262:Adenylyl Cyclases