Neurotensin modulates the binding characteristics of dopamine D2 receptors in rat striatal membranes also following treatment with toluene.
The effects of neurotensin in vitro (1-100 nM) on the binding characteristics of [3H]N-propylnorapomorphine ([3H]NPA) were analysed in striatal membrane preparations of the adult male rat. Subsequently, it was investigated whether the modulatory effects of 10 nM neurotensin on [3H]NPA binding were altered by treatment with toluene in vivo (80 p.p.m., 3 days, 6 h day-1) and in vitro (19 mumol ml-1). Displacement of [3H]NPA binding by raclopride (IC50 about 15 nM) and SCH 23390 (without effect) indicated that [3H]NPA labelled only D2 dopamine receptors in the present study. Neurotensin was found to reduce the affinity of D2 receptors with a maximum response at 10 nM. At this concentration the KD value was increased by 30-40% without any consistent changes in the number of binding sites. The modulatory effect of neurotensin remained intact also following toluene treatment in vivo and in vitro, although at a higher KD range, since toluene alone increased the KD value of [3H]NPA binding by 40-50%. Thus, the mechanisms mediating the effects of neurotensin and toluene on the D2 receptor are likely to be different. When neurotensin and toluene treatments were combined, the KD values of [3H]NPA binding were about twice as high as in non-treated controls. These additive effects may lead to a severely decreased efficiency of dopamine D2-mediated neurotransmission in vivo.
von Euler
G
G
Department of Histology, Karolinska Institute, Stockholm, Sweden.
Fuxe
K
K
Benfenati
F
F
Hansson
T
T
Agnati
L F
LF
Gustafsson
J A
JA
D000818:Animals; D001058:Apomorphine / Q000031:analogs & derivatives / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003342:Corpus Striatum / Q000378:metabolism*; D008297:Male; D009496:Neurotensin / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D017448:Receptors, Dopamine D2; D014050:Toluene / Q000494:pharmacology*
D011954:Receptors, Dopamine; D017448:Receptors, Dopamine D2; D009496:Neurotensin; D014050:Toluene; C009074:N-n-propylnorapomorphine; D001058:Apomorphine