5-hydroxytryptamine-moduline, a new endogenous cerebral peptide, controls the serotonergic activity via its specific interaction with 5-hydroxytryptamine1B/1D receptors - PubMed (original) (raw)
J C Rousselle, M P Fillion, B Grimaldi, I Cloëz-Tayarani, A Fugelli, N Prudhomme, L Seguin, B Rousseau, M Plantefol, R Hen, G Fillion
Affiliations
- PMID: 8863819
Comparative Study
5-hydroxytryptamine-moduline, a new endogenous cerebral peptide, controls the serotonergic activity via its specific interaction with 5-hydroxytryptamine1B/1D receptors
O Massot et al. Mol Pharmacol. 1996 Oct.
Abstract
The serotonergic system controls the activity of neurotransmissions involved in numerous physiological functions. It is also thought to be crucially implicated in various pathologies, including psychiatric disorders such as depression, anxiety, and aggressiveness. The properties of 5-hydroxytryptamine (5-HT)-moduline, a novel endogenous peptide, have been tested in vitro and in vivo. Binding studies have shown that the peptide specifically interacts with 5-HT1B/1D receptors via a noncompetitive mechanism corresponding to a high apparent affinity (EC50 = 10(10) M). The interaction was shown in rat and guinea pig brain tissues and in cells transfected with either 5-HT1B or 5-HT1D beta receptor gene. [3H]5-HT-moduline binds to a single population of sites in mammalian brain (Kd = 0.4 nM in rat, Kd = 0.8 nM in guinea pig) as well as in transfected cells expressing the 5-HT1B or the 5-HT1D beta receptors (Kd = 0.2 and 0.6 nM, respectively). Furthermore, the binding is clearly specific of the LSAL sequence. Autoradiographic studies showed an heterogeneous brain distribution of this site. The interaction of 5-HT-moduline with the 5-HT1B/1D receptor corresponds to a decrease in the functional activity of the receptor (i.e., a decrease in the inhibitory effect of a 5-HT1B agonist on the evoked release of [3H]5-HT from synaptosomal preparation). It was also shown that 5-HT-moduline possess an in vivo effect in the social interaction test in mouse. Finally, it was demonstrated that 5-HT-moduline was released from brain synaptosomal preparation by a K+/Ca(2+)-dependent mechanism. In conclusion, 5-HT-moduline is a novel endogenous peptide regulating the serotonergic activity via a direct action at presynaptic 5-HT receptor. It may play an important role in the physiological mechanisms involving the serotonergic system, particularly in mechanisms corresponding to the elaboration of an appropriate response of the central nervous system to a given stimulus.
Similar articles
- Potential of 5-HT-moduline as a drug target for affective disorders.
Fillion G. Fillion G. Curr Opin Investig Drugs. 2000 Sep;1(1):104-9. Curr Opin Investig Drugs. 2000. PMID: 11249585 Review. - Acute stress induces a differential increase of 5-HT-moduline (LSAL) tissue content in various rat brain areas.
Bonnin A, Grimaldi B, Fillion MP, Fillion G. Bonnin A, et al. Brain Res. 1999 Apr 17;825(1-2):152-60. doi: 10.1016/s0006-8993(99)01265-2. Brain Res. 1999. PMID: 10216182 - Specific interaction of 5-HT-moduline with human 5-HT1b as well as 5-HT1d receptors expressed in transfected cultured cells.
Rousselle JC, Plantefol M, Fillion MP, Massot O, Pauwels PJ, Fillion G. Rousselle JC, et al. Naunyn Schmiedebergs Arch Pharmacol. 1998 Sep;358(3):279-86. doi: 10.1007/pl00005254. Naunyn Schmiedebergs Arch Pharmacol. 1998. PMID: 9774213 - Molecular, cellular and physiological characteristics of 5-HT-moduline, a novel endogenous modulator of 5-HT1B receptor subtype.
Massot O, Rousselle JC, Grimaldi B, Cloëz-Tayarani I, Fillion MP, Plantefol M, Bonnin A, Prudhomme N, Fillion G. Massot O, et al. Ann N Y Acad Sci. 1998 Dec 15;861:174-82. doi: 10.1111/j.1749-6632.1998.tb10189.x. Ann N Y Acad Sci. 1998. PMID: 9928255 Review.
Cited by
- Seven transmembrane receptors as shapeshifting proteins: the impact of allosteric modulation and functional selectivity on new drug discovery.
Kenakin T, Miller LJ. Kenakin T, et al. Pharmacol Rev. 2010 Jun;62(2):265-304. doi: 10.1124/pr.108.000992. Epub 2010 Apr 14. Pharmacol Rev. 2010. PMID: 20392808 Free PMC article. Review. - 5-HT moduline: an endogenous inhibitor of 5-HT(1B/1D)-mediated contraction in pulmonary arteries.
Murdoch R, Morecroft I, MacLean MR. Murdoch R, et al. Br J Pharmacol. 2003 Mar;138(5):795-800. doi: 10.1038/sj.bjp.0705123. Br J Pharmacol. 2003. PMID: 12642380 Free PMC article. - Autoradiographic characterization of [3H]-5-HT-moduline binding sites in rodent brain and their relationship to 5-HT1B receptors.
Cloëz-Tayarani I, Cardona A, Rousselle JC, Massot O, Edelman L, Fillion G. Cloëz-Tayarani I, et al. Proc Natl Acad Sci U S A. 1997 Sep 2;94(18):9899-904. doi: 10.1073/pnas.94.18.9899. Proc Natl Acad Sci U S A. 1997. PMID: 9275223 Free PMC article. - Allosteric Modulators of G Protein-Coupled Dopamine and Serotonin Receptors: A New Class of Atypical Antipsychotics.
Fasciani I, Petragnano F, Aloisi G, Marampon F, Carli M, Scarselli M, Maggio R, Rossi M. Fasciani I, et al. Pharmaceuticals (Basel). 2020 Nov 14;13(11):388. doi: 10.3390/ph13110388. Pharmaceuticals (Basel). 2020. PMID: 33202534 Free PMC article. Review. - Circadian variation in the activity of the 5-HT(1B) autoreceptor in the region of the suprachiasmatic nucleus, measured by microdialysis in the conscious freely-moving rat.
Garabette ML, Martin KF, Redfern PH. Garabette ML, et al. Br J Pharmacol. 2000 Dec;131(8):1569-76. doi: 10.1038/sj.bjp.0703753. Br J Pharmacol. 2000. PMID: 11139433 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous