Neurotensin excitation of serotonergic neurons in the rat nucleus raphe magnus: Ionic and molecular mechanisms

Allen H. Li, Tu Hsueh Yeh, Peter P. Tan, Hwa Min Hwang, Hung Li Wang

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Abstract

To understand the cellular and molecular mechanisms by which neurotensin (NT) induces an analgesic effect in the nucleus raphe magnus (NRM), whole-cell patch-clamp recordings were performed to investigate the electrophysiological effects of NT on acutely dissociated NRM neurons. Two subtypes of neurons, primary serotonergic and secondary non-serotonergic cells, were identified from acutely isolated NRM neurons. During current-clamp recordings, NT depolarized NRM serotonergic neurons and evoked action potentials. Voltage-clamp recordings showed that NT excited serotonergic neurons by enhancing a voltage-insensitive and non-selective cationic conductance. Both SR48692, a selective antagonist of subtype 1 neurotensin receptor (NTR-1), and SR 142948A, a non-selective antagonist of NTR-1 and subtype 2 neurotensin receptor (NTR-2), failed to prevent neurotensin from exciting NRM serotonergic neurons. NT-evoked cationic current was inhibited by the intracellular administration of GDP-β-S. NT failed to induce cationic currents after dialyzing serotonergic neurons with the anti-Gαq/11 antibody. Cellular Ca2+ imaging study using fura-2 showed that NT induced the calcium release from the intracellular store. NT-evoked current was blocked after the internal perfusion of heparin, an IP3 receptor antagonist, or BAPTA, a fast Ca2+ chelator. It is concluded that neurotensin enhancement of the cationic conductance of NRM serotonergic neurons is mediated by a novel subtype of neurotensin receptors. The coupling mechanism via Gαq/11 proteins is likely to involve the generation of IP3, and subsequent IP3-evoked Ca2+ release from intracellular stores results in activating the non-selective cationic conductance.

Original languageEnglish
Pages (from-to)1073-1083
Number of pages11
JournalNeuropharmacology
Volume40
Issue number8
DOIs
Publication statusPublished - Jun 23 2001
Externally publishedYes

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Keywords

  • G proteins
  • Inositol (1,4,5) trisphosphate
  • Neurotensin
  • Non-selective cationic currents
  • Nucleus raphe magnus
  • Serotonergic neuron

ASJC Scopus subject areas

  • Pharmacology
  • Cellular and Molecular Neuroscience

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