DAMGO binding to mouse brain membranes: Influence of salts, guanine nucleotides, substance P, and substance P fragments

Solveig A. Krumins, Duckhee C. Kim, Orisa J. Igwe, Alice A. Larson

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

Substance P (SP) appears to mediate many processes of the central nervous system, including pain. This report deals with modulation of opioid binding in the mouse brain by SP and SP fragments, as well as by salts and guanine nucleotides. Binding studies of the selective μ opioid receptor agonist [d-Ala2,MePhe4,Gly(ol)5]enkephalin (DAMGO) to mouse brain membrane preparations demonstrated that guanine nucleotide modulation of DAMGO binding affinity was modified by SP. However, SP had little or no influence on inhibition of DAMGO binding induced by salts, such as MgCl2, CaCl2, or NaCl. By replacing GTP with GppNHp, SP (0.1 nM) produced multiple affinity forms of the DAMGO receptor, while at a higher concentration (10 nM), SP lost its influence on DAMGO binding. Furthermore, 0.1 nM SP changed DAMGO binding parameters in a medium containing NaCl, CaCl2, and GppNHp such that the high- and low-affinity conformations of the receptor converted to a single site following the addition of SP to the incubation medium. While the C-terminal SP fragment SP(5-11) was without effect, the N-terminal SP fragments SP(1-9) and SP(1-7) appeared to imitate SP in modifying GppNHp-modulated DAMGO binding. These results suggest that SP functions as a modulator of opioid binding at the μ receptor and it appears that the N-terminus of SP plays a role in the modulatory process.

Original languageEnglish (US)
Pages (from-to)309-314
Number of pages6
JournalPeptides
Volume14
Issue number2
DOIs
StatePublished - Jan 1 1993

Keywords

  • Binding
  • Modulation
  • Opioid receptors
  • Substance P
  • Substance P amino-terminal fragments

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