Esquifino A I, Selgas L, Della Maggiore V, Castrillón P O, Cardinali D P
Departamento de Bioquímica y Biología Molecular III, Facultad de Medicina, Universidad Complutense, Madrid, Spain.
Eur J Pharmacol. 1997 Jan 29;319(2-3):181-9. doi: 10.1016/s0014-2999(96)00853-9.
Diurnal changes in cyclosporine efficacy to affect ornithine decarboxylase activity, [3H]norepinephrine uptake and [3H]choline conversion into [3H]acetylcholine were examined in rat submaxillary lymph nodes. Cyclosporine (5 or 20 mg/kg) caused a dose-dependent decrease in lymph node ornithine decarboxylase, being active at 5 or 20 mg/kg in Freund's adjuvant-treated rats, and at 20 mg/kg in rats treated with the adjuvant's vehicle. In immunized rats the lower cyclosporine dose was ineffective when injected during the night. Cyclosporine increased lymph node [3H]norepinephrine uptake dose dependently, with significant differences between the 20 mg/kg dose and controls in vehicle-treated rats and between 5 or 20 mg/kg and controls in Freund's adjuvant-treated rats. In immunized rats, 5 mg/kg cyclosporine increased [3H]norepinephrine uptake when injected at 13:00 or 17:00 h. Both doses of cyclosporine augmented lymph node synthesis of [3H]acetylcholine to a similar extent. In immunized and non-immunized rats cyclosporine suppressed the diurnal rhythm of lymph node adrenergic and cholinergic activity found in controls. After unilateral sympathetic denervation (by superior cervical ganglionectomy) and/or unilateral parasympathetic decentralization (by chorda tympani section), cyclosporine (5 mg/kg) decreased Freund's adjuvant-induced activation of lymph node ornithine decarboxylase when injected at 17:00 or 01:00 h. On the sham-operated side, cyclosporine was effective when injected at 17:00 h only. Decentralization, or a combined ganglionectomy plus decentralization, decreased lymph node ornithine decarboxylase activity. The results active regulation of the effects of cyclosporine in submaxillary lymph nodes by local autonomic nerves.
在大鼠下颌下淋巴结中研究了环孢素影响鸟氨酸脱羧酶活性、[3H]去甲肾上腺素摄取以及[3H]胆碱转化为[3H]乙酰胆碱的疗效的昼夜变化。环孢素（5或20mg/kg）导致淋巴结鸟氨酸脱羧酶呈剂量依赖性降低，在弗氏佐剂处理的大鼠中5或20mg/kg时具有活性，在佐剂赋形剂处理的大鼠中20mg/kg时具有活性。在免疫大鼠中，较低剂量的环孢素在夜间注射时无效。环孢素剂量依赖性地增加淋巴结[3H]去甲肾上腺素摄取，在赋形剂处理的大鼠中20mg/kg剂量与对照组之间以及在弗氏佐剂处理的大鼠中5或20mg/kg与对照组之间存在显著差异。在免疫大鼠中，5mg/kg环孢素在13:00或17:00注射时增加[3H]去甲肾上腺素摄取。两种剂量的环孢素在相似程度上增强了淋巴结[3H]乙酰胆碱的合成。在免疫和未免疫大鼠中，环孢素抑制了对照组中发现的淋巴结肾上腺素能和胆碱能活性的昼夜节律。在单侧交感神经去神经支配（通过颈上神经节切除术）和/或单侧副交感神经去传入（通过鼓索切断术）后，环孢素（5mg/kg）在17:00或01:00注射时降低了弗氏佐剂诱导的淋巴结鸟氨酸脱羧酶的激活。在假手术侧，环孢素仅在17:00注射时有效。去传入或联合神经节切除术加去传入降低了淋巴结鸟氨酸脱羧酶活性。结果表明局部自主神经对环孢素在下颌下淋巴结中的作用具有积极调节作用。
