Rapid endocytosis of a G protein-coupled receptor: Substance P-evoked internalization of its receptor in the rat striatum in vivo

Patrick W. Mantyh, Clark J. Allen, Joseph R. Ghilardi, Scott D. Rogers, Christopher R. Mantyh, Hantao Liu, Allan I. Basbaum, Steven R. Vigna, John E. Maggio

Research output: Contribution to journalArticle

262 Scopus citations

Abstract

Studies on cultured cells have shown that agonists induce several types of G protein-coupled receptors to undergo internalization. We have investigated this phenomenon in rat striatum, using substance P (SP)-induced internalization of the SP receptor (SPR) as our model system. Within i min of a unilateral striatal injection of SP in the anesthetized rat, nearly 60% of the SPR-immunoreactive neurons within the injection zone display massive internalization of the SPR-i.e. 20-200 SPR+ endosomes per cell body. Within the dendrites the SPR undergoes a striking translocation from the plasma membrane to endosomes, and these dendrites also undergo a morphological reorganization, changing from a structure of rather uniform diameter to one characterized by large, swollen varicosities connected by thin fibers. In both cell bodies and dendrites the number of SPR+ endosomes returns to baseline within 60 min of SP injection. The number of neurons displaying substantial endosomal SPR internalization is dependent on the concentration of injected SP, and the SP-induced SPR internalization is inhibited by the nonpeptide neurokinin 1 receptor antagonist RP-67,580. These data demonstrate that in the central nervous system in vivo, SP induces a rapid and widespread SPR internalization in the cell bodies and dendrites and a structural reorganization of the dendrites. These results suggest that many of the observations that have been made on the internalization and recycling of G protein-coupled receptors in in vitro transfected cell systems are applicable to similar events that occur in the mammalian central nervous system in vivo.

Original languageEnglish (US)
Pages (from-to)2622-2626
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number7
DOIs
StatePublished - Mar 28 1995

Keywords

  • central nervous system
  • desensitization
  • neurokinin 1 receptor
  • receptor-mediated endocytosis
  • substance P receptor

ASJC Scopus subject areas

  • General

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