Newman M E, Shapira B, Lerer B
Yaacov Herzog Centre for Brain and Psychiatry Research, Ezrath Nashim Hospital, Jerusalem, Israel.
Neuropharmacology. 1991 Dec;30(12A):1297-301. doi: 10.1016/0028-3908(91)90026-8.
The effects of chronic administration of lithium, short-term administration of lithium, chronic administration of DMI and a combination of short-term administration of lithium and chronic administration of DMI on second messenger responses were studied in the hippocampus of the rat. Lithium reduced the ability of carbachol to inhibit forskolin-stimulated activity of adenylate cyclase in hippocampal membranes but had no effect on carbachol-stimulated formation of inositol phosphate in hippocampal slices. Lithium, however, reduced the degree of stimulation of formation of inositol phosphate, induced by noradrenaline. Desimipramine alone did not affect carbachol- or noradrenaline-mediated reactions and a combination of short-term administration of lithium and chronic administration of DMI did not potentiate the action of lithium on adenylate cyclase. Both lithium and DMI abolished the inhibition by 5-HT of carbachol-stimulated formation of inositol phosphate a 5-HT1A receptor-mediated response. It is concluded that the chronic effects of administration of lithium may be related to actions at the G protein level and that different modes of coupling of receptors to G proteins may be responsible for the variety of effects observed.
在大鼠海马体中研究了长期给予锂、短期给予锂、长期给予地昔帕明以及短期给予锂与长期给予地昔帕明联合使用对第二信使反应的影响。锂降低了卡巴胆碱抑制海马体膜中福斯高林刺激的腺苷酸环化酶活性的能力，但对海马体切片中卡巴胆碱刺激的肌醇磷酸形成没有影响。然而，锂降低了去甲肾上腺素诱导的肌醇磷酸形成的刺激程度。单独使用地昔帕明不影响卡巴胆碱或去甲肾上腺素介导的反应，短期给予锂与长期给予地昔帕明联合使用也不会增强锂对腺苷酸环化酶的作用。锂和地昔帕明都消除了5-羟色胺对卡巴胆碱刺激的肌醇磷酸形成的抑制作用，这是一种5-HT1A受体介导的反应。得出的结论是，锂给药的长期影响可能与G蛋白水平的作用有关，并且受体与G蛋白的不同偶联模式可能是观察到的各种效应的原因。
