Modulation of [3H]DAGO binding by substance P (SP) and SP fragments in the mouse brain and spinal cord via MU1 interactions

S. A. Krumins, D. C. Kim, Virginia S Seybold, Alice A Larson

Research output: Contribution to journalArticlepeer-review

21 Scopus citations

Abstract

Binding of [3H]DAGO to fresh, frozen or β-funaltrexamine (β-FNA) pretreated membranes of mouse brain and spinal cord was extensively studied using substance P (SP) or SP fragments as potential competitors and/or modulators. The objective was to determine whether SP exerts its analgesic effect by interacting with μ opioid receptors. The affinity of DAGO was reduced and binding capacity was increased in the presence of SP or the N-terminal SP fragments SP(1-9) and SP(1-4) but not the C-terminal SP fragment SP(5-11). Because sub-nanomolar concentrations of SP or N-terminal SP fragments displaced [3H] DAGO binding to a minor but detectable degree, it is suggested that SP interacts with μ1 sites through its N-terminus portion. The effect of SP on DAGO binding was less in the spinal cord compared to the rest of the brain. Modulation of DAGO binding by SP was enhanced in the brain after pretreatment of membranes with the narcotic antagonist β-FNA. These results suggest a novel mechanism for the analgesic action of SP.

Original languageEnglish (US)
Pages (from-to)225-233
Number of pages9
JournalNeuropeptides
Volume13
Issue number4
DOIs
StatePublished - Jan 1 1989

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