Brain neurotensin receptors in mice bred for differences in sensitivity to ethanol.
The hypothesis that some of ethanol's acute effects are mediated via neurotensinergic systems was investigated by characterizing neurotensin (NT) receptors in mice (LS and SS) selectively bred for differences in sensitivity to ethanol. [3H]Neurotensin binding in brain membranes from both mouse lines was specific, saturable, reversible, and linear with protein concentrations. Subcellular localization studies showed specific NT binding to be concentrated in the microsomal/synaptosomal fractions. Scatchard analyses of [3H]NT binding indicated similar KD values for membranes from various brain regions of LS and SS mice. However, Bmax values in frontal cortex, cerebellum, and striatum were greater in SS than in LS mice. In competitive binding studies IC50 values were lower for NT8-13 than for NT1-13, and IC50 values for NT1-8, NT1-11, D-Trp11-NT, and D-Tyr11-NT were greater than 1000 nM. Association and dissociation rate constants for [3H]NT and resulting KD values (0.8 nM) were similar for LS and SS brain membranes. Ethanol, in vitro, had no effect on NT binding characteristics, but as expected various cations markedly increased KD values.
Erwin
V G
VG
Alcohol Research Center, School of Pharmacy, University of Colorado, Boulder 80309.
Korte
A
A
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects*; D000431:Ethanol / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009496:Neurotensin / Q000378:metabolism*; D018028:Receptors, Neurotensin; D017981:Receptors, Neurotransmitter / Q000187:drug effects* / Q000235:genetics; D012894:Sleep Stages / Q000187:drug effects*; D013347:Subcellular Fractions / Q000187:drug effects
D018028:Receptors, Neurotensin; D017981:Receptors, Neurotransmitter; D009496:Neurotensin; D000431:Ethanol