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Effects of polycationic peptides of different natures on the functional state of the serotonin-regulated adenylate cyclase system in the rat brain

Content Provider	Springer Nature Link
Author	Shpakov, A. O. Gur’yav, I. A. Tarasenko, I. I. Vlasov, G. P.
Copyright Year	2009
Abstract	In animals of different phylogenetic levels, polycationic peptides are one of the most important regulators of the functional activities of hormonal signaling systems, including the adenylate cyclase signaling system (AC system). We compared the functional state of the AC system in the rat brain after treatment with three synthetic polycationic peptides (C-ɛAhx-YKAKKKKKKKWK (I), CK(C$_{10}$)-ɛAhx-YKAKKKKKKKWK (II), and (NH$_{2}$)$_{64}$(K)$_{32}$(K)$_{16}$(K)$_{8}$(K)$_{4}$(K)$_{2}$KA (III)) and the peptide toxin mastoparan, which do not have homology to signaling proteins, and the synthetic polycationic peptides ARERKATKTL$^{255–264}$K (IV) and HSRKALKASL$^{306–315}$K (V), which are derivatives of the C-terminal domains of the third cytoplasmic loop of the 1B and 6 serotonin receptors (SR). We found that the peptides I, II, and III stimulated heterotrimeric G-proteins of both the stimulating (G$_{s}$) and inhibiting (G$_{i}$) type, peptide IV and, mastoparan predominantly affected G$_{i}$-proteins, and peptide V mainly activated G$_{s}$-proteins. Peptides II and V stimulated basal AC activity, while mastoparan and peptides III and IV inhibited the forskolin-stimulated activity of the enzyme. The serotonin-induced stimulation of AC strongly decreased in the presence of peptide V, a derivative of SR of the sixth type coupled with G$_{s}$-proteins (the efficacy of the inhibitory effect of the peptides was V > II > III > IV ≅ mastoparan ≅ I). Inhibition of the AC system by serotonin decreased in the presence of peptide IV, a derivative of 1B SR coupled with G$_{i}$-proteins (the efficacy of inhibition was IV > III ≅ mastoparan > II ≥ I ≅ V). Inhibition of AC by the D$_{2}$-agonist bromocriptine strongly decreased in the presence of mastoparan and peptide III, and peptide IV was less active (mastoparan ≥ III > IV > II > I ≅ V). Among the polycationic peptides studied peptides IV and V and SR derivatives caused the strongest inhibition of serotonin-stimulated GTP binding and specific binding of the hormone with membranes, and their effect was observed at a concentration of 10$^{−6}$ M. Thus, in contrast to polycationic peptides that have no homology with signal proteins, the polycationic peptides and SR derivatives selectively affected the functional state of the AC system regulated by serotonin in the rat brain and transmission of hormonal signals.
Starting Page	272
Ending Page	281
Page Count	10
File Format	PDF
ISSN	18197124
Journal	Neurochemical Journal
Volume Number	3
Issue Number	4
e-ISSN	18197132
Language	English
Publisher	SP MAIK Nauka/Interperiodica
Publisher Date	2009-12-17
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	adenylate cyclase adenylate cyclase signaling system G-protein mastoparan brain polycationic peptide serotonin serotonin receptors cytoplasmic loop Neurosciences
Content Type	Text
Resource Type	Article
Subject	Molecular Biology Biochemistry Cellular and Molecular Neuroscience

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