Li Q, Battaglia G, Van de Kar L D
Department of Pharmacology, Stritch School of Medicine, Loyola University Chicago, IL 60153, USA.
Brain Res. 1997 Sep 19;769(1):141-51. doi: 10.1016/s0006-8993(97)00693-8.
The present study examined the distribution of [3H]8-OH-DPAT-labeled 5-HT1A receptors and their degree of coupling to G proteins in the hypothalamus and several other brain regions. In addition, we also investigated the effects of repeated injections of fluoxetine on the density and G protein coupling of 5-HT1A receptors in hypothalamic nuclei and other brain regions using autoradiography. Male rats received daily injections of either fluoxetine (10 mg/kg, ip) for 3, 7, 14 and 22 days, or saline for 22 days. 5-HT1A receptors were labeled by 2 nM [3H]8-hydroxy-2-(dipropylamino)tetralin ([3H]8-OH-DPAT) in the absence or presence of guanylylimidodiphosphate (Gpp(NH)p, 10[-5] M) to determine the percentage of 5-HT1A receptors coupled to G proteins. 5-HT1A receptor densities ranged from 7 to 63 fmol/mg tissue equivalent among hypothalamic nuclei. Similarly, the degree of G protein coupling to 5-HT1A receptors varied markedly among hypothalamic nuclei (from 14% to 61%) and among other brain regions (from 17% to 85%). Fluoxetine did not alter the density or the degree of coupling of 5-HT1A receptors in any brain regions. These data indicate marked regional differences in the degree of G protein-coupled 5-HT1A receptors and suggest that fluoxetine-induced desensitization of hypothalamic 5-HT1A receptors is not mediated by changes in receptor density or G protein coupling.
本研究检测了下丘脑及其他几个脑区中[3H]8-OH-DPAT标记的5-HT1A受体的分布及其与G蛋白的偶联程度。此外，我们还使用放射自显影技术研究了反复注射氟西汀对下丘脑核及其他脑区中5-HT1A受体密度和G蛋白偶联的影响。雄性大鼠每日注射氟西汀（10mg/kg，腹腔注射），持续3、7、14和22天，或注射生理盐水，持续22天。在不存在或存在鸟苷酰亚胺二磷酸（Gpp(NH)p，10[-5]M）的情况下，用2nM[3H]8-羟基-2-（二丙基氨基）四氢萘（[3H]8-OH-DPAT）标记5-HT1A受体，以确定与G蛋白偶联的5-HT1A受体的百分比。下丘脑核中5-HT1A受体密度在7至63fmol/mg组织当量之间。同样，下丘脑核之间（从14%至61%）以及其他脑区之间（从17%至85%），G蛋白与5-HT1A受体的偶联程度差异显著。氟西汀未改变任何脑区中5-HT1A受体的密度或偶联程度。这些数据表明G蛋白偶联的5-HT1A受体程度存在显著的区域差异，并提示氟西汀诱导的下丘脑5-HT1A受体脱敏不是由受体密度或G蛋白偶联的变化介导的。
