Lima L, Sourkes T L
J Pharmacol Exp Ther. 1986 Apr;237(1):265-70.
The administration of oxotremorine together with methylatropine to rats produces a dose-dependent increase of adrenal dopamine-beta-hydroxylase (DBH) activity. This effect is abolished by denervation of the gland and by cycloheximide. The Km for tyramine is not affected by the trans-synaptic induction of DBH by oxotremorine. The induction is selective, because similar treatment does not affect adrenal dopa decarboxylase or lactate dehydrogenase in the adrenal gland. The combination of 6-hydroxydopamine i.c.v. or propranolol i.p. does not alter the effect of oxotremorine on adrenal DBH. However, propranolol reduces the tremorigenic action of the muscarinic agonist. The systemic administration of p-chlorophenylalanine or the i.c.v. injection of 5,7-dihydroxytryptamine before oxotremorine treatment does not affect the increase of adrenal DBH. Progabide, gamma-aminobutyric acid, a (GABA)A and GABAB receptor agonist that effectively crosses the blood-brain barrier, reduces the effect of oxotremorine in a dose-dependent manner. Muscimol given by either of two routes, i.c.v. at a constant rate (Alzet minipump) or i.p., produces significant decreases of adrenal DBH activity and attenuates the action of oxotremorine. Denervation of the gland abolishes the effect of muscimol i.p. in decreasing adrenal DBH activity. Baclofen, a GABAB receptor agonist, has no effect by itself or does it affect the action of oxotremorine. None of these GABA agonists has any in vitro effect on adrenal DBH activity. Bicuculline, GABAA receptor antagonist, reverses the action of progabide in oxotremorine-treated rats with respect to adrenal DBH activity, partially blocks the effect of muscimol and enhances the increase obtained with oxotremorine.(ABSTRACT TRUNCATED AT 250 WORDS)
将氧代震颤素与甲基阿托品一起给予大鼠，会使肾上腺多巴胺-β-羟化酶（DBH）活性呈剂量依赖性增加。这种效应会因腺体去神经支配和环己酰亚胺而消除。酪胺的米氏常数不受氧代震颤素对DBH的跨突触诱导的影响。这种诱导具有选择性，因为类似的处理不会影响肾上腺多巴脱羧酶或肾上腺中的乳酸脱氢酶。脑室内注射6-羟基多巴胺或腹腔注射普萘洛尔不会改变氧代震颤素对肾上腺DBH的作用。然而，普萘洛尔会降低毒蕈碱激动剂的致震颤作用。在氧代震颤素处理前全身给予对氯苯丙氨酸或脑室内注射5,7-二羟基色胺不会影响肾上腺DBH的增加。普罗加比，一种能有效穿过血脑屏障的γ-氨基丁酸（GABA）A和GABAB受体激动剂，以剂量依赖性方式降低氧代震颤素的作用。通过两种途径之一给予蝇蕈醇，即以恒定速率通过脑室内注射（Alzet微型泵）或腹腔注射，会使肾上腺DBH活性显著降低，并减弱氧代震颤素的作用。腺体去神经支配会消除腹腔注射蝇蕈醇降低肾上腺DBH活性的作用。巴氯芬，一种GABAB受体激动剂，自身无作用，也不影响氧代震颤素的作用。这些GABA激动剂在体外对肾上腺DBH活性均无任何影响。GABAA受体拮抗剂荷包牡丹碱可逆转普罗加比在氧代震颤素处理的大鼠中对肾上腺DBH活性的作用，部分阻断蝇蕈醇的作用，并增强氧代震颤素所导致的增加。（摘要截断于250字）
