Premium
Structural Requirements of 5‐Hydroxytryptamine‐Moduline Analogues to Interact with the 5‐Hydroxytryptamine 1B Receptor
Author(s) -
Plantefol Mathieu,
Rousselle Jean Claude,
Massot Olivier,
Bernardi Elizabeth,
Schoofs Alain René,
Pourrias Bernard,
Ollivier Roland,
Fillion Gilles
Publication year - 1999
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1999.0732617.x
Subject(s) - tetrapeptide , peptide , amino acid , stereochemistry , serine , chemistry , receptor , binding site , biochemistry , enzyme
: 5‐Hydroxytryptamine‐moduline is an endogenous cerebral tetrapeptide that regulates the activity of 5‐hydroxytryptamine 1B receptors. Direct binding of 5‐[ 3 H]hydroxytryptamine‐moduline on rat brain homogenate evidenced the existence of two interacting sites for the peptide, very likely corresponding to different conformations of the 5‐hydroxytryptamine 1B receptor : The peptide first binds to a low‐affinity state of the receptor (pIC 50 = 7.68 ± 0.14) and then induces (or stabilizes) a high‐affinity complex (pIC 50 = 11.62 ± 0.18). This work focuses on the ability of 5‐hydroxytryptamine‐moduline analogues to recognize the high‐ and low‐affinity sites for 5‐hydroxytryptamine‐moduline. The results obtained show that the two conformers of the 5‐hydroxytryptamine 1B receptor have similar but not identical binding pockets for 5‐hydroxytryptamine‐moduline. These two sites proved to be stereoselective and selective for tetrapeptides and favored the binding of peptides with hydrophobic amino acids in positions 1 and 4, serine in position 2, and a short amino acid in position 3. However, the serine in position 2 seems to be more important for the interaction of the peptide with the low‐affinity site than the high‐affinity one, which only needs a short hydrophobic amino acid in position 2.