The C-terminal neurotensin-(8-13) fragment potently modulates rat neostriatal dopamine D2 receptors.
The effects of neurotensin fragments and of neurotensin itself on the characteristics of neostriatal dopamine D2 agonist binding were studied in competition experiments with dopamine using the D2 antagonist, [3H]raclopride. The biologically active neurotensin-(8-13) fragment, but not the inactive neurotensin-(1-7) fragment, caused a concentration-related increase in the KH and KL values of dopamine with a maximal increase by 110 and 97%, respectively, at 1 nM, while neurotensin-(1-13) only induced such changes at 10 nM. In view of the higher potency and the increased ability of neurotensin-(8-13) versus neurotensin (1-13) to reduce the affinities of the high- and low-affinity states of the neostriatal D2 receptors, the C-terminal neurotensin fragments may be among the endogenous ligands of the neostriatal neurotensin receptors.
Li
X M
XM
Department of Histology and Neurobiology, Karolinska Institutet, Stockholm, Sweden.
Von Euler
G
G
Hedlund
P B
PB
Finnman
U B
UB
Fuxe
K
K
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D017072:Neostriatum / Q000187:drug effects* / Q000378:metabolism; D009496:Neurotensin / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D020891:Raclopride; D011869:Radioligand Assay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000187:drug effects* / Q000378:metabolism; D012457:Salicylamides / Q000378:metabolism
D010446:Peptide Fragments; D017448:Receptors, Dopamine D2; D012457:Salicylamides; D009496:Neurotensin; D020891:Raclopride; C054381:neurotensin (8-13)