Synaptic relationship between substance P and the substance P receptor: Light and electron microscopic characterization of the mismatch between neuropeptides and their receptors

Hantao Liu, Jessica L. Brown, Luc Jasmin, John E. Maggio, Steven R. Vigna, Patrick W. Mantyh, Allan I. Basbaum

Research output: Contribution to journalArticlepeer-review

262 Scopus citations

Abstract

Light microscopic studies have demonstrated significant mismatches in the location of neuropeptides and their respective binding sites in the central nervous system. In the present study we used an antiserum raised against a synthetic peptide corresponding to the carboxyl-terminal tail of the substance P (SP) receptor (SPR) to further explore the relationship between a neuropeptide and its receptor. Light microscopy revealed an excellent correlation between the patterns of SPR immunoreactivity and of 125I- labeled SPR-binding sites in the central nervous system. The SPR appeared to be exclusively expressed by neurons; in fact, the SPR decorates the somatic and dendritic surface of neurons, producing Golgi-like images. Electron microscopic analysis in cortex, striatum, and spinal cord revealed that approximately 70% of the surface membrane of immunoreactive neurons is SPR laden. Simultaneous electron microscopic labeling of SP and SPR demonstrated significant mismatch at the synaptic level. Although some SP terminals contacted SPR-immunoreactive membrane, no more than 15% of the SPR-laden membrane apposed synaptic terminals. These results suggest that in contrast to more 'classical' central and peripheral nervous system synapses, wherein the receptor immediately apposes the site of neurotransmitter storage and release, much of the surface of SPR-expressing neurons can be targeted by SP that diffuses a considerable distance from its site of release.

Original languageEnglish (US)
Pages (from-to)1009-1013
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume91
Issue number3
DOIs
StatePublished - Feb 1 1994

ASJC Scopus subject areas

  • General

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