Cornil Charlotte A, Castelino Christina B, Ball Gregory F
Department of Psychological and Brain Sciences, Johns Hopkins University, Baltimore, MD 21218, USA.
J Chem Neuroanat. 2008 Mar;35(2):202-15. doi: 10.1016/j.jchemneu.2007.10.004. Epub 2007 Nov 4.
A commonly held view is that dopamine exerts its effects via binding to D1- and D2-dopaminergic receptors. However, recent data have emerged supporting the existence of a direct interaction of dopamine with adrenergic but this interaction has been poorly investigated. In this study, the pharmacological basis of possible in vivo interactions between dopamine and alpha(2)-adrenergic receptors was investigated in zebra finches. A binding competition study showed that dopamine displaces the binding of the alpha(2)-adrenergic ligand, [(3)H]RX821002, in the brain. The affinity of dopamine for the adrenergic sites does not differ between the sexes and is 10- to 28-fold lower than that for norepinephrine. To assess the anatomical distribution of this interaction, binding competitions were performed on brain slices incubated in 5nM [(3)H]RX821002 in the absence of any competitor or in the presence of norepinephrine [0.1microM] or dopamine [1microM]. Both norepinephrine and dopamine displaced the binding of the radioligand though to a different extent in most of the regions studied (e.g., area X, the lateral part of the magnocellular nucleus of anterior nidopallium, HVC, arcopallium dorsale, ventral tegmental area and substantia grisea centralis) but not in the robust nucleus of the arcopallium. Together these data provide evidence for a direct interaction between dopamine and adrenergic receptors in songbird brains albeit with regional variation.
一种普遍的观点是多巴胺通过与D1和D2多巴胺能受体结合发挥作用。然而,最近有数据支持多巴胺与肾上腺素能受体存在直接相互作用,但这种相互作用的研究较少。在本研究中,在斑胸草雀体内研究了多巴胺与α(2)-肾上腺素能受体可能的相互作用的药理学基础。结合竞争研究表明,多巴胺可取代脑中α(2)-肾上腺素能配体[(3)H]RX821002的结合。多巴胺对肾上腺素能位点的亲和力在两性之间没有差异,且比对去甲肾上腺素的亲和力低10至28倍。为了评估这种相互作用的解剖分布,在不存在任何竞争者或存在去甲肾上腺素[0.1μM]或多巴胺[1μM]的情况下,对在5nM[(3)H]RX821002中孵育的脑切片进行结合竞争实验。在大多数研究区域(例如X区、前巢核大细胞外侧部、HVC、背侧古皮质、腹侧被盖区和中央灰质),去甲肾上腺素和多巴胺都能取代放射性配体的结合,但在古皮质的粗壮核中则不能。这些数据共同为鸣禽脑中多巴胺与肾上腺素能受体之间的直接相互作用提供了证据,尽管存在区域差异。