Garcia M, Floran B, Arias-Montaño J A, Young J M, Aceves J
Departamento de Fisiologia, Biofisica y Neurociencias, Centro de Investigacion y de Estudios Avanzados del IPN, Mexico D.F.
Neuroscience. 1997 Sep;80(1):241-9. doi: 10.1016/s0306-4522(97)00100-0.
The release of [3H]GABA from slices of rat substantia nigra pars reticulata induced by increasing extracellular K+ from 6 to 15 mM in the presence of 10 microM sulpiride was inhibited by 73 +/- 3% by 1 microM SCH 23390, consistent with a large component of release dependent upon D1 receptor activation. The histamine H3 receptor-selective agonist immepip (1 microM) and the non-selective agonist histamine (100 microM) inhibited [3H]GABA release by 78 +/- 2 and 80 +/- 2%, respectively. The inhibition by both agonists was reversed by the H3 receptor antagonist thioperamide (1 microM). However, in the presence of 1 microM SCH 23390 depolarization-induced release of [3H]GABA was not significantly decreased by 1 microM immepip. In rats depleted of dopamine by pretreatment with reserpine, immepip no longer inhibited control release of [3H]GABA, but in the presence of 1 microM SKF 38393, which produced a 7 +/- 1-fold stimulation of release, immepip reduced the release to a level not statistically different from that in the presence of immepip alone. Immepip (1 microM) also inhibited the depolarization-induced release of [3H]dopamine from substantia nigra pars reticulata slices, by 38 +/- 3%. The evidence is consistent with the proposition that activation of histamine H3 receptors leads to the selective inhibition of the component of depolarization-induced [3H]GABA release in substantia nigra pars reticulata slices which is dependent upon D1 receptor activation. This appears to be largely an action at the terminals of the striatonigral GABA projection neurons, which may be enhanced by a partial inhibition of dendritic [3H]dopamine release.
在存在10微摩尔舒必利的情况下，将细胞外钾离子浓度从6毫摩尔增加到15毫摩尔可诱导大鼠黑质网状部切片释放[3H]GABA，1微摩尔SCH 23390可使其释放受到73±3%的抑制，这与很大一部分释放依赖于D1受体激活相一致。组胺H3受体选择性激动剂依美哌啶（1微摩尔）和非选择性激动剂组胺（100微摩尔）分别使[3H]GABA释放受到78±2%和80±2%的抑制。两种激动剂的抑制作用均被H3受体拮抗剂硫代哌啶（1微摩尔）逆转。然而，在存在1微摩尔SCH 23390的情况下，1微摩尔依美哌啶并未使去极化诱导的[3H]GABA释放显著减少。在用利血平预处理使多巴胺耗竭的大鼠中，依美哌啶不再抑制[3H]GABA的对照释放，但在存在1微摩尔SKF 38393（可使释放增加7±1倍）的情况下，依美哌啶将释放降低到与仅存在依美哌啶时无统计学差异的水平。依美哌啶（1微摩尔）还使黑质网状部切片中去极化诱导的[3H]多巴胺释放受到38±3%的抑制。该证据与组胺H3受体激活导致黑质网状部切片中依赖于D1受体激活的去极化诱导的[3H]GABA释放成分受到选择性抑制的观点一致。这似乎主要是在纹状体黑质GABA投射神经元的终末起作用，可能通过对树突状[3H]多巴胺释放的部分抑制而增强。
