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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