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 f rom rat brain which interacts specifically with 5-HT1B/1D receptors. T he binding interaction of 5-HT-Moduline with 5-HT1B/1D receptors appea red to be a non-competitive process, since the B-max value of [I-125] cyanopindolol binding on rat brain cortical membranes was decreased wi thout modification of the K-d. This interaction was conserved on NIH 3 T3 cells expressing the 5-HT1B receptor (IC50=10(-11)M) suggesting tha t the binding site for 5-HT-Moduline is localized on the 5-HT1B recept or protein. The observed interaction may lead to functional alteration s 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).