Yoshioka M, Matsumoto M, Togashi H, Smith C B, Saito H
First Department of Pharmacology, Hokkaido University School of Medicine, Sapporo, Japan.
Neurosci Lett. 1992 May 11;139(1):53-6. doi: 10.1016/0304-3940(92)90856-3.
The purpose of the present study is to clarify the modulation of the biosynthesis of serotonin (5-HT) via the alpha 2-adrenoceptors in the brain. For this purpose, 5-hydroxytryptophan (5-HTP) accumulation was determined using an HPLC-ECD system in the presence of the inhibition of aromatic L-amino acid decarboxylase. Administration of alpha 2-adrenoceptor agonist, clonidine, produced a reduction of the in vivo 5-HTP accumulation in both the rat hippocampus and dorsal raphe nucleus. In addition, alpha 2-adrenoceptor antagonist, idazoxan, increased the 5-HTP accumulation in both the hippocampus and the dorsal raphe nucleus. In rats with catecholaminergic neurons denervated by pretreatment with 6-hydroxydopamine, clonidine failed to produce a reduction of 5-HTP accumulation in the dorsal raphe nucleus. On the other hand, hippocampal 5-HTP accumulation was decreased significantly. Brain tryptophan levels were unaffected by either clonidine or idazoxan. These results suggest that alpha 2-adrenoceptors might modulate serotonin biosynthesis and this modulation might be related to the neuroanatomical differences in the rat brain.
本研究的目的是阐明大脑中α2 -肾上腺素能受体对血清素（5 -羟色胺，5 - HT）生物合成的调节作用。为此，在抑制芳香族L -氨基酸脱羧酶的情况下，使用高效液相色谱 - 电化学检测系统（HPLC - ECD）测定5 -羟色氨酸（5 - HTP）的积累量。给予α2 -肾上腺素能受体激动剂可乐定后，大鼠海马体和中缝背核中的体内5 - HTP积累量均降低。此外，α2 -肾上腺素能受体拮抗剂咪唑克生增加了海马体和中缝背核中的5 - HTP积累量。在用6 -羟基多巴胺预处理使儿茶酚胺能神经元去神经支配的大鼠中，可乐定未能使中缝背核中的5 - HTP积累量降低。另一方面，海马体中的5 - HTP积累量显著下降。大脑色氨酸水平不受可乐定或咪唑克生的影响。这些结果表明，α2 -肾上腺素能受体可能调节血清素的生物合成，并且这种调节可能与大鼠大脑中的神经解剖学差异有关。
