Diurnal changes in cyclosporine effect on ornithine decarboxylase and noradrenergic and cholinergic activities in submaxillary lymph nodes.
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.
Esquifino
A I
AI
Departamento de Bioquímica y Biología Molecular III, Facultad de Medicina, Universidad Complutense, Madrid, Spain. pelayos@eucmax.sim.ucm.es
Selgas
L
L
Della Maggiore
V
V
Castrillón
P O
PO
Cardinali
D P
DP
D000818:Animals; D002794:Choline / Q000378:metabolism; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology*; D016572:Cyclosporine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008198:Lymph Nodes / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism*; D008297:Male; D009638:Norepinephrine / Q000378:metabolism / Q000502:physiology; D009955:Ornithine Decarboxylase / Q000378:metabolism*; D017764:Parasympathectomy; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013562:Sympathectomy; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009955:Ornithine Decarboxylase; D002794:Choline; D009638:Norepinephrine