Neurotensin modulates central muscarinic receptors, an effect which does not involve the high affinity neurotensin receptor (NTS1).

P. G. SCHNEIDER; M. G. LÓPEZ ORDIERES; G. RODRÍGUEZ DE LORES ARNAIZ

REGULATORY PEPTIDES

ELSEVIER SCIENCE BV

Año: 2010 vol. 163 p. 37 - 42

0167-0115

Neurotensin (NT) is a tridecapeptide distributed in central and peripheral nervous system, which can behave as a neurotransmitter or neuromodulator at central and peripheral levels. Herein we tested the potential effect of this peptide on quinuclidinyl benzilate ([3H]-QNB) binding to muscarinic receptor in rat CNS membranes. It was observed that NT decreased up to 50-70 % ligand binding at 1 x 10-7 M - 1 x 10-5 M concentration in cerebral cortex, cerebellum and striatum. In hippocampus, NT exerted a biphasic effect, behaving as an stimulator in the presence of 1 x 10-12 M - 1 x 10-10 M concentration but as an inhibitor at 1 x 10-8 M - 1 x 10-5 M concentration. In order to test the involvement of high affinity NT receptor (NTS1) in NT inhibitory effect, assays were carried out in the presence of 1 x 10-6 M NT and / or SR 48692 (Sanofi-Aventis, U.S., Inc.), a specific antagonist for this receptor, dissolved in dimethylsulfoxide (DMSO) 10% v / v. As controls, membranes incubated with DMSO and / or NT 1 x 10-6 M plus DMSO were processed. It was found that NT + DMSO decreased [3H]-QNB binding to cerebral cortex, cerebellum and hippocampal membranes by 49%, 32% and 53%, respectively. This inhibition was not observed with the DMSO control group. Membranes preincubation with 1 x 10-6 M SR 48692 failed to alter NT effect on binding. SR 48692 at 1 x 10-6 M concentration decreased the binding by 50% only in cerebral cortex membranes, suggesting a possible direct effect of the antagonist on muscarinic receptors in this area. It was therefore concluded that the high affinity NT receptor may not be involved in ligand binding inhibition to muscarinic receptor by NT.