Seguin L, Seznec J C, Fillion G
Unité de Pharmacologie Neuro-immuno-endocrinienne, Institut Pasteur, Paris, France.
Neurosci Res. 1997 Mar;27(3):277-80. doi: 10.1016/s0168-0102(96)01150-9.
5-HT-moduline (Leu-Ser-Ala-Leu, LSAL) is a novel endogenous peptide isolated from rat brain which interacts in vitro specifically with 5-HT(1B) receptors by a non-competitive mechanism. In the present study, we demonstrate that the efficacy of the selective 5-HT(1B) receptor agonist CP 93 129 in inhibiting the forskolin-stimulated adenylyl cyclase activity in the rat substantia nigra was reduced 15 min after intracerebral injection of LSAL compared to vehicle or ALLS (scrambled peptide) injected rats. Accordingly, the concentration-response curve of the agonist is shifted to the right with a 3.5-fold increase of the half-maximal inhibitory concentration compared to vehicle injected rats. Thus, the in vivo desensitization of serotonergic autoreceptors strongly strengthens the important role of 5-HT-moduline in the rapid adaptative control of the serotonergic system, implicated in numerous pathological events as anxiety and depression.
5-羟色胺调节素（亮氨酸-丝氨酸-丙氨酸-亮氨酸，LSAL）是一种从大鼠脑中分离出的新型内源性肽，它在体外通过非竞争性机制与5-羟色胺（1B）受体特异性相互作用。在本研究中，我们证明，与注射赋形剂或ALLS（乱序肽）的大鼠相比，脑内注射LSAL 15分钟后，选择性5-羟色胺（1B）受体激动剂CP 93 129抑制大鼠黑质中福斯高林刺激的腺苷酸环化酶活性的效力降低。因此，与注射赋形剂的大鼠相比，激动剂的浓度-反应曲线右移，半数最大抑制浓度增加3.5倍。因此，5-羟色胺能自身受体的体内脱敏有力地强化了5-羟色胺调节素在5-羟色胺能系统快速适应性控制中的重要作用，这与包括焦虑和抑郁在内的许多病理事件有关。
