A new peptide, 5-HT-moduline, isolated and purified from mammalian brain specifically interacts with 5-HT1B/1D receptors.
5-HT-Moduline (Leu-Ser-Ala-Leu) is a new endogenous peptide purified from rat brain which interacts specifically with 5-HT1B/1D receptors. The binding interaction of 5-HT-Moduline with 5-HT1B/1D receptors appeared to be a non-competitive process, since the Bmax value of [125I] cyanopindolol binding on rat brain cortical membranes was decreased without modification of the Kd. This interaction was conserved on NIH 3T3 cells expressing the 5-HT1B receptor (IC50 = 10(-11)M) suggesting that the binding site for 5-HT-Moduline is localized on the 5-HT1B receptor protein. The observed interaction may lead to functional alterations of 5-HT1B/1D receptors known to play an important role in regulating the release of 5-HT from serotonergic nerve terminals (autoreceptors) as well as the release of other neurotransmitters (heteroreceptors).
Fillion
G
G
Unité de Pharmacologie Neuro-Immuno-Endocrinienne, Institut Pasteur, Paris, France.
Rousselle
J C
JC
Massot
O
O
Zifa
E
E
Fillion
M P
MP
Prudhomme
N
N
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001923:Brain Chemistry / Q000502:physiology*; D002460:Cell Line; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D066298:In Vitro Techniques; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000302:isolation & purification / Q000494:pharmacology*; D009842:Oligopeptides / Q000302:isolation & purification / Q000494:pharmacology*; D010869:Pindolol / Q000031:analogs & derivatives; D051381:Rats; D011985:Receptors, Serotonin / Q000187:drug effects*
C102005:5-HT-moduline; D009479:Neuropeptides; D009842:Oligopeptides; D011985:Receptors, Serotonin; C047975:cyanopindolol; D010869:Pindolol