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Molecular Pharmacology

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Abstract

5-hydroxytryptamine-moduline, a new endogenous cerebral peptide, controls the serotonergic activity via its specific interaction with 5-hydroxytryptamine1B/1D receptors.

O Massot, J C Rousselle, M P Fillion, B Grimaldi, I Cloëz-Tayarani, A Fugelli, N Prudhomme, L Seguin, B Rousseau, M Plantefol, R Hen and G Fillion
Molecular Pharmacology October 1996, 50 (4) 752-762;
O Massot
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J C Rousselle
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M P Fillion
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B Grimaldi
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I Cloëz-Tayarani
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A Fugelli
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N Prudhomme
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L Seguin
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B Rousseau
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M Plantefol
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R Hen
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G Fillion
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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.

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Molecular Pharmacology
Vol. 50, Issue 4
1 Oct 1996
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Abstract

5-hydroxytryptamine-moduline, a new endogenous cerebral peptide, controls the serotonergic activity via its specific interaction with 5-hydroxytryptamine1B/1D receptors.

O Massot, J C Rousselle, M P Fillion, B Grimaldi, I Cloëz-Tayarani, A Fugelli, N Prudhomme, L Seguin, B Rousseau, M Plantefol, R Hen and G Fillion
Molecular Pharmacology October 1, 1996, 50 (4) 752-762;

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Abstract

5-hydroxytryptamine-moduline, a new endogenous cerebral peptide, controls the serotonergic activity via its specific interaction with 5-hydroxytryptamine1B/1D receptors.

O Massot, J C Rousselle, M P Fillion, B Grimaldi, I Cloëz-Tayarani, A Fugelli, N Prudhomme, L Seguin, B Rousseau, M Plantefol, R Hen and G Fillion
Molecular Pharmacology October 1, 1996, 50 (4) 752-762;
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