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

Research output: Contribution to journalArticle

29 Citations (Scopus)

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

Fingerprint

Serotonergic Neurons
Neurotensin
Neurotensin Receptors
Gq-G11 GTP-Binding Protein alpha Subunits
Nucleus Raphe Magnus
Inositol 1,4,5-Trisphosphate Receptors
Neurons
Fura-2
Chelating Agents
Evoked Potentials
Action Potentials
Analgesics
Perfusion
Calcium

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

Cite this

Neurotensin excitation of serotonergic neurons in the rat nucleus raphe magnus : Ionic and molecular mechanisms. / Li, Allen H.; Yeh, Tu Hsueh; Tan, Peter P.; Hwang, Hwa Min; Wang, Hung Li.

In: Neuropharmacology, Vol. 40, No. 8, 23.06.2001, p. 1073-1083.

Research output: Contribution to journalArticle

Li, Allen H. ; Yeh, Tu Hsueh ; Tan, Peter P. ; Hwang, Hwa Min ; Wang, Hung Li. / Neurotensin excitation of serotonergic neurons in the rat nucleus raphe magnus : Ionic and molecular mechanisms. In: Neuropharmacology. 2001 ; Vol. 40, No. 8. pp. 1073-1083.
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