caa a22 4500 605536872 CHVBK 20210128100854.0 cr unu---uuuuu 210128e20151101xx s 000 0 eng 10.1007/s10517-015-3093-4 doi (NATIONALLICENCE)springer-10.1007/s10517-015-3093-4 Regulation of the Melanocortin-Sensitive Adenylate Cyclase System by N-Acylated Peptide 71-82 of Type 4 Melanocortin Receptor [Elektronische Daten] [A. Shpakov, K. Derkach, E. Shpakova] The peptides structurally corresponding in to cytoplasmic loops of G protein-coupled receptors (GPCR) are able to control functional activity of homologous receptors and the corresponding signaling pathways. Modification of these peptides with hydrophobic radicals enhances their biological activity due to penetration of lipophilic derivatives through the membrane and anchoring near their targets, GPCR. We synthesized an N-palmitoylated peptide Palm-Val-[Lys-Asn-Lys-Asn-Leu-His-Ser-Pro-(Nle)-Tyr-Phe-Phe71-82]-amide-Palm-Val-(71-82) structurally corresponding to cytoplasmic loop 1 of melanocortin 4 receptor (M4R). We found that in micromolar concentrations it very effectively suppresses stimulation of basal adenylate cyclase activity and basal level of GppNHp binding of heterotrimeric G proteins produced by THIQ and α-melanocyte stimulating hormone (α-MSH), agonists of M4R homologous to the peptide, in synaptosomal membranes of rat brain. The peptide Palm-Val-(71-82) also reduced, albeit to a significantly less extent, stimulation of adenylate cyclase and G-proteins by M3R agonist of γ-MSH, due to high homology of the peptide primary structure to M3R cytoplasmic loop 1. The synthesized peptide with activity of M4R/M3R antagonist can be used for the development of regulators of M4R and M3R and the corresponding biochemical and physiological processes. Springer Science+Business Media New York, 2015 adenylate cyclase nationallicence melanocortin receptor nationallicence brain nationallicence peptide nationallicence cytoplasmic loop 1 nationallicence Shpakov A. Laboratory of Molecular Endocrinology, I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia aut Derkach K. Laboratory of Molecular Endocrinology, I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia aut Shpakova E. Laboratory of Molecular Endocrinology, I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia aut Bulletin of Experimental Biology and Medicine Springer US; http://www.springer-ny.com 160/1(2015-11-01), 40-44 0007-4888 160:1<40 2015 160 10517 https://doi.org/10.1007/s10517-015-3093-4 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s10517-015-3093-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Shpakov A. Laboratory of Molecular Endocrinology, I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia aut NATIONALLICENCE 700 1- Derkach K. Laboratory of Molecular Endocrinology, I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia aut NATIONALLICENCE 700 1- Shpakova E. Laboratory of Molecular Endocrinology, I. M. Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, St. Petersburg, Russia aut NATIONALLICENCE 773 0- Bulletin of Experimental Biology and Medicine Springer US; http://www.springer-ny.com 160/1(2015-11-01), 40-44 0007-4888 160:1<40 2015 160 10517