Yamada M, Yamada M, Lombet A, Forgez P, Rostène W
INSERM U339, Hôpital Saint-Antoine, Paris, France.
Life Sci. 1998;62(23):PL 375-80. doi: 10.1016/s0024-3205(98)00192-1.
Neurotensin has been shown to produce pharmacological effects both in brain and periphery. Several of these effects are mediated by a high-affinity neurotensin NT1 receptor. On the other hand, a low-affinity levocabastine-sensitive neurotensin NT2 receptor was molecularly cloned from rodent brain recently. In this study, in contrast to NT1 receptor, levocabastine (a histamine H1 receptor antagonist) and SR48692 (an antagonist for NT1 receptor) strongly stimulated intracellular Ca2+ mobilization in transfected Chinese hamster ovary cells expressing rat NT2 receptor, thus acting as potent NT2 receptor. Furthermore, despite of their affinities for NT2 receptor, the Ca2+ responses to potent NT1 agonists, neurotensin or JMV449 ([Lys8-(CH2NH)-Lys9]Pro-Tyr-Ile-Leu, a peptidase resistant analogue of neurotensin) were much smaller than that observed with SR48692. These findings suggest that NT1 and NT2 receptors present distinct functional characteristics and that SR48692 may act as a potent agonist for NT2 receptor.
神经降压素已被证明在大脑和外周均能产生药理作用。其中一些作用是由高亲和力的神经降压素NT1受体介导的。另一方面，低亲和力的对左卡巴斯汀敏感的神经降压素NT2受体最近已从啮齿动物大脑中被分子克隆出来。在本研究中，与NT1受体不同，左卡巴斯汀（一种组胺H1受体拮抗剂）和SR48692（一种NT1受体拮抗剂）在表达大鼠NT2受体的转染中国仓鼠卵巢细胞中强烈刺激细胞内Ca2+动员，因此作为有效的NT2受体起作用。此外，尽管它们对NT2受体有亲和力，但对强效NT1激动剂神经降压素或JMV449（[Lys8-(CH2NH)-Lys9]Pro-Tyr-Ile-Leu，一种神经降压素的肽酶抗性类似物）的Ca2+反应远小于用SR48692观察到的反应。这些发现表明NT1和NT2受体具有不同的功能特征，并且SR48692可能作为NT2受体的强效激动剂起作用。
