The endogenous cerebral tetrapeptide 5-HT-moduline reduces in vivo the functional activity of central 5-HT1B receptors in the rat.
5-HT-moduline (Leu-Ser-Ala-Leu, LSAL) is a novel endogenous peptide isolated from rat brain which interacts in vitro specifically with 5-HT(1B) receptors by a non-competitive mechanism. In the present study, we demonstrate that the efficacy of the selective 5-HT(1B) receptor agonist CP 93 129 in inhibiting the forskolin-stimulated adenylyl cyclase activity in the rat substantia nigra was reduced 15 min after intracerebral injection of LSAL compared to vehicle or ALLS (scrambled peptide) injected rats. Accordingly, the concentration-response curve of the agonist is shifted to the right with a 3.5-fold increase of the half-maximal inhibitory concentration compared to vehicle injected rats. Thus, the in vivo desensitization of serotonergic autoreceptors strongly strengthens the important role of 5-HT-moduline in the rapid adaptative control of the serotonergic system, implicated in numerous pathological events as anxiety and depression.
Seguin
L
L
Unité de Pharmacologie Neuro-immuno-endocrinienne, Institut Pasteur, Paris, France.
Seznec
J C
JC
Fillion
G
G
D000818:Animals; D001921:Brain / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011985:Receptors, Serotonin / Q000187:drug effects*
C102005:5-HT-moduline; D009479:Neuropeptides; D009842:Oligopeptides; D011725:Pyridines; D011758:Pyrroles; D011985:Receptors, Serotonin; C065046:3-(1,2,5,6-tetrahydropyrid-4-yl)pyrrolo(3,2-b)pyrid-5-one