Chemistry: molecular biology and microbiology – Measuring or testing process involving enzymes or... – Involving antigen-antibody binding – specific binding protein...
Patent
1995-04-14
1998-07-14
Allen, Marianne P.
Chemistry: molecular biology and microbiology
Measuring or testing process involving enzymes or...
Involving antigen-antibody binding, specific binding protein...
530350, 536 235, 435325, 4352523, 4353201, C12N 1500
Patent
active
057802459
DESCRIPTION:
BRIEF SUMMARY
The present invention relates to new polypeptides and to the genetic material permitting their expression. More especially, it relates to new polypeptides having serotoninergic receptor activity.
Serotonin is a neuromodulator capable of inducing and modulating a wide variety of behavioural functions such as sleep, appetite, locomotion, sexual activity and vascular contraction. It is accepted that serotonin activity is mediated by its interaction with receptors, designated serotoninergic receptors or 5-HT (for 5-hydroxytryptamine) receptors. Molecular biology studies as well as pharmacological studies have revealed the existence of a large number of subtypes of 5-HT receptors. The 5-HT receptors which have been described to date belong either to the family of receptors associated with ion channels (5-HT3 receptors), or to the family of receptors which interact with G proteins and which possess seven transmembrane domains. Moreover, analysis of the amino acid sequences has shown that the 5-HT receptors which interact with G proteins may be subdivided into two distinct groups: 5HT1 receptors, comprising the mammalian subtypes 5HT1A, 5HT1B and 5HT1D, as well as three drosophila 5HT receptors; and 5HT2 receptors comprising the subtypes 5HT2 and 5HT1C.
These receptors are doubtless not the only 5HT receptors which exist, inasmuch as pharmacological studies have revealed other subtypes, such as 5HT4 receptors as well as some receptors related to the subtype 5HT1 ("5HT1-like" receptors). Furthermore, additional molecular biology studies have also revealed heterogeneities within the subtypes 5HT1B/1D.
Nowadays, contrary to the other subtypes, the 5HT2 receptors have not been widely studied. The 5HT2 receptors act via phospholipase C, and are responsible for numerous physiological activities of serotonin at the central and peripheral level. At the cardiovascular level, they are involved in the contraction of the blood vessels and in the morphological changes of the platelets; in the central nervous system, they act on the sensitization of the neurones to tactile stimuli and on the mediation of the hallucinogenic effects of diethylamidelysergic acid, and of the related phenylisopropylamines.
Numerous studies show that the 5HT2 receptors described up until now do not account for all the properties which are attributed to them. In particular, certain 5HT2-types effects of serotonin on the peripheral smooth muscles are classified as atypical effects, of which the effects are thought to be mediated by unknown receptors.
The present invention is the outcome of the demonstration of new polypeptides having serotoninergic receptor activity. While belonging to the family of receptors which interact with G proteins, these new polypeptides differ from the serotoninergic receptors already described (5HT1, 5HT2, 5HT3 and 5HT4) from both a structural standpoint and a pharmacological standpoint. More especially, the invention is the outcome of the isolation and characterization of these new polypeptides, designated 5HT2C, and also of the genetic material permitting their expression or identification. Pharmacological study of these receptors show that they could account for the atypical effects of serotonin which were previously observed.
A first subject of the invention hence lies in polypeptides comprising all or part of the peptide sequence SEQ ID No. 2 or of a derivative of the latter.
For the purposes of the present invention, the term derivative denotes any molecule obtained by modification, of a genetic and/or chemical nature, of the peptide sequence SEQ ID No. 2. Modification of a genetic and/or chemical nature may be understood to mean any mutation, substitution, deletion, addition and/or modification of one or more residues. Such derivatives may be generated for different purposes, such as, in particular, that of increasing the affinity of the peptide for its ligand(s), that of improving its levels of production, that of increasing its resistance to proteases, that of increasing and/or modifying its activity or that of end
REFERENCES:
EMBO J. 11(9):3481-87, 1992, Foguet Hoyer Pardo Parekh Kluxen et al., Cloning and functional characterization of the rat stomach fundus serotonin.
Dec. 31, 1991 Biochem. Biophys. Res. Commun. 181(3):1469-78, Saltzman Morse Whitman Ivanshchenko Jaye Felder, Cloning of the Human Serotonin 5-HT2 and 5-HT1C Receptor Subtypes.
FEBS Lett. 312(2,3): 203-07, Nov. 1992, Loric Launay Colas Maroteaux, New mouse 5-HT2-like receptor Expression in brain, heart and intestine.
Trends in Pharmacol. Sci. 10:64-69, 1989, Hartig, Molecular biology of 5-HT receptors.
Neuro Report 3:345-348, 1992, Foguet Nguyen Le Lubbert, Structure of the mouse 5-HT 1C, 5-HT2 and stomach fundus serotonin receptor genes.
Pharmacol. Rev. 44:401-458, 1992, Zifa Fillion, 5-Hydroxytryptamine Receptors.
Mol. Pharmacol. 42:549-57, 1992, Kursar Nelson Wainscott Cohen Baez, Molecular Cloning, Functional Expression, and Pharmacological Characterization of a Novel Serotonin Receptor (5-Hydroxytryptamine.sub.2F) from Rat Stomach Fundus.
Pharm. Rev. 46(2):157-203, 1994, Hoyer Clarke Fozard Hartig Martin et al., International Union of Pharmacology Classification of Receptors for 5-Hydroxytryptamine (Serotonin).
Allen Marianne P.
Institut National de la Sante et de la Recherche Medicale
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