Increase in neurotensin receptor expression in rat brain induced by chronic treatment with the nonpeptide neurotensin receptor antagonist SR 48692.
In the present study, we examined the regulation of neurotensin receptor following a chronic pharmacological blockade of the neurotensin transmission with a nonpeptide neurotensin receptor antagonist, SR 48692. Our results showed that treatment of the rats for five days with SR 48692, at a dose of 1 mg/kg, i.p., induced an increase of both the number of binding sites for 125I-neurotensin to whole brain membrane homogenates and neurotensin receptor mRNA levels in the ventral mesencephalon. This study brings the first evidence for an in vivo up-regulation of neurotensin receptors following their pharmacological blockade, and suggests that endogenous neurotensin exerts a tonic inhibitory control on neurotensin receptor mRNA levels.
Azzi
M
M
INSERM U339, Hôpital Saint-Antoine, Paris, France.
Nicot
A
A
Gully
D
D
Kitabgi
P
P
Bérod
A
A
Rostène
W
W
D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive / Q000187:drug effects; D001923:Brain Chemistry / Q000187:drug effects*; D003720:Densitometry; D017403:In Situ Hybridization; D066298:In Vitro Techniques; D007457:Iodine Radioisotopes; D008297:Male; D008566:Membranes / Q000187:drug effects / Q000378:metabolism; D009496:Neurotensin / Q000493:pharmacokinetics; D011720:Pyrazoles / Q000494:pharmacology*; D011804:Quinolines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D018028:Receptors, Neurotensin / Q000037:antagonists & inhibitors* / Q000096:biosynthesis*
D007457:Iodine Radioisotopes; D011720:Pyrazoles; D011804:Quinolines; D012333:RNA, Messenger; D018028:Receptors, Neurotensin; C079087:SR 48692; D009496:Neurotensin