ISOLATION AND CHARACTERIZATION OF AN ENDOGENOUS PEPTIDE FROM RAT-BRAIN INTERACTING SPECIFICALLY WITH THE SEROTONERGIC 1B RECEPTOR SUBTYPES

The existence of endogenous compounds interacting with the serotonergi c system was previously postulated, In the present work, rat brain tis sues were extracted by acidic and organic procedures, The resulting ex tract was tested for its capacity to interact with the binding of [H-3 ]5-hydroxytryptamine ([H-3]5-HT) to 5-HT1 receptors, Compounds respons ible for the observed inhibitory activities were isolated and purified by high pressure liquid chromatography, A tetrapeptide corresponding to a novel amino acid sequence Leu-Ser-Ala-Leu (LSAL) was identified, It re duces the binding of [H-3]5-HT to 5-HT1 receptors at low concent ration (IC50 = 10(-10) M), This effect corresponds to a specific inter action at 5-HT1B receptors since LSAL does not significantly affect ot her neurotransmitter bindings, LSAL appears heterogeneously distribute d throughout the brain (hippocampus > cerebellum > striatum > brain st em) and in peripheral tissues (kidney > lung > stomach > blood > liver > spleen). Two other peptides, Leu-Ser (LS) and Ala-Leu (AL), were al so purified, They hardly affected [H-3]5-HT binding compared with LSAL , They presumably represent degradation products of the functional pep tide LSAL. The fact that LSAL interacts specifically with 5-HT1B recep tors that inhibit the release of neurotransmitters and particularly th at of 5-HT itself suggests that this peptide may be involved in mechan isms controlling 5-HT neurotransmission and, accordingly, may play an important role in pathophysiological functions related to 5-HT activit y.