Peptides derived from the third cytoplasmatic loop of serotonin 1B receptor subtype selectively inhibit serotonin signal transduction via a homologous receptor

• Published in: Rossiiskii fiziologicheskii zhurnal imeni I.M. Sechenova Vol. 96; no. 11; p. 1062
• Main Authors: Shpakov, A O, Shpakova, E A, Tarasenko, I I, Derkach, K V, Chistiakova, O V, Vlasov, G P
• Format: Journal Article
• Language: Russian
• Published: Russia (Federation) 01-11-2010
• Subjects: Adenylyl Cyclases - metabolism; Animals; Brain - drug effects; Brain - enzymology; Colforsin - pharmacology; GTP-Binding Proteins - metabolism; Guanosine Triphosphate - metabolism; In Vitro Techniques; Male; Oligopeptides - chemical synthesis; Oligopeptides - pharmacology; Protein Binding; Rats; Rats, Wistar; Receptor, Serotonin, 5-HT1B - chemistry; Receptor, Serotonin, 5-HT1B - physiology; Serotonin - physiology; Serotonin Antagonists - pharmacology; Serotonin Receptor Agonists - pharmacology; Signal Transduction - drug effects; Synaptosomes - drug effects; Synaptosomes - metabolism
• ISSN: 0869-8139

The third intracellular loops of hormonal receptors play the main role in the interaction of majority of the serpentine type receptors with heterotrimeric G-proteins. In recent years, it was shown that synthetic peptides corresponding to membrane-proximal regions of these loops could be selectively influenced with hormonal signal transduction via the receptors homologous to them and trigger signalling cascade in absence of the hormone. For the first time, we succeeded in synthesizing the peptides derived from C-terminal region of the third intracellular loop of the IB-subtype serotonin receptor and studied their influence on serotonin-sensitive adenylyl cyclase system in the rat brain. The peptides 300-316 and 306-316 (the numbers correspond to amino acid positions in the rat IB-subtype serotonin receptor) at micromolar concentrations in absence of hormone-stimulated GTP-binding of Gi,-proteins coupled with the IB-subtype serotonin receptors and inhibited forskolin-stimulated adenylyl cyclase activity. Using selective agonists and antagonists of serotonin receptors it was shown that the peptides 300-316 and 306--316 inhibited serotonin signal transduction via homologous to them receptor and weakly influenced other types of serotonin receptors. The peptide 300-316 is more active compared with its shorter analogue 306-316 in the selectivity and efficiency of action on adenylyl cyclase signalling system regulated via the IB-subtype serotonin receptors. These findings indicate that the regions 300-316 of the IB-subtype serotonin receptor are involved in interaction with Grproteins and consist of the main molecular determinants responsible for serotonin signal transduction to adenylyl cyclase.