Tomiyama Katsunori, McNamara Fergal N, Clifford Jeremiah J, Kinsella Anthony, Drago John, Fuchs Sara, Grandy David K, Low Malcolm J, Rubinstein Marcelo, Tighe Orna, Croke David T, Koshikawa Noriaki, Waddington John L
Department of Clinical Pharmacology and Institute of Biopharmaceutical Sciences, Royal College of Surgeons in Ireland, St Stephen's Green, Dublin 2, Ireland.
Synapse. 2004 Jan;51(1):71-81. doi: 10.1002/syn.10284.
Using a novel system, the role of D2-like dopamine receptors in distinct topographies of orofacial movement was assessed in mutant mice with congenic D2 vs. D3 receptor knockout, and compared with findings in D1A mutants. Under spontaneous conditions, D2 mutants evidenced increased vertical jaw movements and unaltered horizontal jaw movements, with reductions in tongue protrusions and incisor chattering; in D3 mutants, only incisor chattering was reduced. Given previous evidence that D1A mutants show reduced horizontal but not vertical jaw movements, this indicates that apparent oppositional D1-like:D2-like interactions in the regulation of composited jaw movements may in fact reflect the independent actions of D2 receptors to inhibit vertical jaw movements and of D1A receptors to facilitate horizontal jaw movements. Effects of the D2-like agonist RU 24213 to exert greater reduction in horizontal than in vertical jaw movements were not altered prominently in either D2 or D3 mutants. The D1-like agonists A 68930 and SK&F 83959 induced vertical jaw movements, tongue protrusions, and incisor chattering; induction of tongue protrusions by A 68930 was reduced in D2 mutants. D2 receptors exert topographically specific regulation of orofacial movements in a manner distinct from their D1A counterparts, while D3 receptors exert only minor regulation of such movements.
利用一种新型系统,在同基因D2与D3受体敲除的突变小鼠中评估了D2样多巴胺受体在口面部运动不同拓扑结构中的作用,并与D1A突变体的研究结果进行了比较。在自发条件下,D2突变体表现出垂直颌运动增加,水平颌运动未改变,同时舌突出和切牙颤动减少;在D3突变体中,只有切牙颤动减少。鉴于先前有证据表明D1A突变体的水平颌运动减少但垂直颌运动未减少,这表明在复合颌运动调节中明显相反的D1样:D2样相互作用实际上可能反映了D2受体抑制垂直颌运动和D1A受体促进水平颌运动的独立作用。D2样激动剂RU 24213对水平颌运动的减少作用大于对垂直颌运动的减少作用,在D2或D3突变体中均未显著改变。D1样激动剂A 68930和SK&F 83959诱导垂直颌运动、舌突出和切牙颤动;在D2突变体中,A 68930诱导的舌突出减少。D2受体以与其D1A对应物不同的方式对口面部运动进行拓扑特异性调节,而D3受体对此类运动仅发挥轻微调节作用。