Differential expression of two isoforms of the neurokinin-1 (substance P) receptor in vivo

Patrick W. Mantyh, Scott D. Rogers, Joseph R. Ghilardi, John E. Maggio, Christopher R. Mantyh, Steven R. Vigna

Research output: Contribution to journalArticle

50 Scopus citations

Abstract

Recent pharmacological and biochemical studies have suggested that there may be more than one molecular form of the neurokinin-1 receptor (NK-1), a long and short isoform differing in the length of their cytoplasmic carboxyl-terminal tails, but no definitive evidence of the existence of such NK-1 receptor isoforms in tissue has been presented. To examine whether these different isoforms are expressed in vivo we have compared the distribution of high affinity substance P (SP) binding sites (visualized by autoradiography with [125I]SP), with the distribution of the C-terminal epitope of the full length receptor (visualized with a specific antibody against the extreme C-terminal sequence). The former method labels both long and short forms of the NK-1 receptor, while the latter labels only the long form of the protein. In the rat there is a close correspondence of[125I]SP binding and NK-1 immunoreactivity in the striatum, suggesting that the long isoform predominates in this tissue. In the parotid and submaxillary gland, there are very high levels of [[125I]SP binding but only low levels of NK-1 immunoreactivity, suggesting that expression of the short form predominates in these tissues. These results imply that different tissues express different ratios of the two isoforms of the NK-1 receptor. This differential expression provides the theoretical basis for tissue specific pharmacological targeting of NK-1 receptors.

Original languageEnglish (US)
Pages (from-to)8-13
Number of pages6
JournalBrain Research
Volume719
Issue number1-2
DOIs
StatePublished - May 6 1996
Externally publishedYes

Keywords

  • G-Protein coupled receptor
  • Immunocytochemistry
  • Neurokinin-1
  • Parotid
  • Receptor autoradiography
  • Receptor heterogeneity
  • Striatum
  • Submaxillary
  • Substance P
  • Tachykinin

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Clinical Neurology
  • Developmental Biology

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