Booze R M, Crisostomo E A, Davis J N
Department of Medicine (Neurology), Duke University Medical Center, Durham, North Carolina.
J Pharmacol Exp Ther. 1989 Jun;249(3):911-20.
The localization and number of beta adrenergic receptors were directly compared in the brains of rats and guinea pigs. The time course of association and saturability of [125I]cyanopindolol (CYP) binding to slide-mounted tissue sections was similar in rats (Kd = 17 pM) and guinea pigs (Kd = 20 pM). The beta-1 and beta-2 receptor subtypes were examined through the use of highly selective unlabeled receptor antagonists, ICI 118,551 (50 nM) and ICI 89,406 (70 nM). Dramatic species differences between rats and guinea pigs were observed in the neuroanatomical regional localization of the beta adrenergic receptor subtypes. For example, in the thalamus prominent beta-1 and beta-2 receptor populations were identified in the rat; however, the entire thalamus of the guinea pig had few, if any, beta adrenergic receptors of either subtype. Hippocampal area CA1 had high levels of beta-2 adrenergic receptors in both rats and guinea pigs but was accompanied by a widespread distribution of beta-2 adrenergic receptors only in rats. Quantitative autoradiographic analyses of 25 selected neuroanatomical regions 1) confirmed the qualitative differences in CNS beta adrenergic receptor localization, 2) determined that guinea pigs had significantly lower levels of beta adrenergic receptors than rats and 3) indicated a differential pattern of receptor subtypes between the two species. Knowledge of species differences in receptor patterns may be useful in designing effective experiments as well as in exploring the relationships between receptor and innervation patterns. Collectively, these data suggest caution be used in extrapolation of the relationships of neurotransmitters and receptors from studies of a single species.
对大鼠和豚鼠大脑中的β-肾上腺素能受体的定位和数量进行了直接比较。[¹²⁵I]氰吲哚洛尔(CYP)与载玻片上组织切片结合的结合时间进程和饱和性在大鼠(Kd = 17 pM)和豚鼠(Kd = 20 pM)中相似。通过使用高度选择性的未标记受体拮抗剂ICI 118,551(50 nM)和ICI 89,406(70 nM)对β-1和β-2受体亚型进行了检测。在β-肾上腺素能受体亚型的神经解剖区域定位方面,观察到大鼠和豚鼠之间存在显著的物种差异。例如,在大鼠的丘脑中可识别出突出的β-1和β-2受体群体;然而,豚鼠的整个丘脑几乎没有(如果有的话)任何一种亚型的β-肾上腺素能受体。海马CA1区在大鼠和豚鼠中都有高水平的β-2肾上腺素能受体,但仅在大鼠中伴有β-2肾上腺素能受体的广泛分布。对25个选定神经解剖区域的定量放射自显影分析:1)证实了中枢神经系统β-肾上腺素能受体定位的定性差异,2)确定豚鼠的β-肾上腺素能受体水平明显低于大鼠,3)表明了两种物种之间受体亚型的差异模式。了解受体模式的物种差异可能有助于设计有效的实验以及探索受体与神经支配模式之间的关系。总体而言,这些数据表明在从单一物种的研究中推断神经递质和受体的关系时应谨慎。