Modulation of [3H]DAGO binding by substance P (SP) and SP fragments in the mouse brain and spinal cord via MU1 interactions.
Binding of [3H]DAGO to fresh, frozen or beta-funaltrexamine (beta-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 mu 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 mu 1 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 beta-FNA. These results suggest a novel mechanism for the analgesic action of SP.
Krumins
S A
SA
Dept. Cell Biol. & Neuroanat., University of Minnesota, Minneapolis 55455.
Kim
D C
DC
Seybold
V S
VS
Larson
A A
AA
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism* / Q000648:ultrastructure; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D046508:Culture Techniques; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000378:metabolism*; D005615:Freezing; D051379:Mice; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D010446:Peptide Fragments / Q000378:metabolism*; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism*; D017450:Receptors, Opioid, mu; D013116:Spinal Cord / Q000378:metabolism* / Q000648:ultrastructure; D013373:Substance P / Q000378:metabolism* / Q000502:physiology
D004745:Enkephalins; D010446:Peptide Fragments; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D013373:Substance P; D009271:Naltrexone; C024524:beta-funaltrexamine