非肽类神经降压素受体拮抗剂SR 48692长期处理诱导大鼠脑内神经降压素受体表达增加。

Increase in neurotensin receptor expression in rat brain induced by chronic treatment with the nonpeptide neurotensin receptor antagonist SR 48692.

作者信息

Azzi M, Nicot A, Gully D, Kitabgi P, Bérod A, Rostène W

机构信息

INSERM U339, Hôpital Saint-Antoine, Paris, France.

出版信息

Neurosci Lett. 1994 May 19;172(1-2):97-100. doi: 10.1016/0304-3940(94)90671-8.

DOI:10.1016/0304-3940(94)90671-8

PMID:8084546

Abstract

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.

摘要

在本研究中，我们使用非肽类神经降压素受体拮抗剂SR 48692对神经降压素传递进行慢性药理阻断后，检测了神经降压素受体的调节情况。我们的结果显示，以1 mg/kg的剂量腹腔注射SR 48692对大鼠进行为期五天的治疗，可导致全脑膜匀浆中125I-神经降压素结合位点的数量以及腹侧中脑中神经降压素受体mRNA水平均增加。该研究首次证明了神经降压素受体在药理阻断后会在体内上调，并表明内源性神经降压素对神经降压素受体mRNA水平发挥着持续性的抑制作用。