Kujacic M, Carlsson A
Department of Pharmacology, University of Göteborg, Sweden.
Eur J Pharmacol. 1995 May 4;278(1):9-15. doi: 10.1016/0014-2999(95)00092-y.
Using adrenal dopamine as indicator we have previously obtained evidence that quinpirole and several other agonists on dopamine D2-like receptors acutely stimulate the synthesis of adrenal catecholamines. In the present study we measured the effect of quinpirole and dopamine on the hydroxylation of tyrosine in the adrenals, using the method of DOPA (3,4-dihydroxyphenylalanine) accumulation following the administration of the inhibitor of aromatic L-amino acid decarboxylase NSD 1015 (3-hydroxybenzylhydrazyne). In view of the large amounts of catecholamines in the adrenal tissue samples, this necessitated a modification of the method for analysing DOPA. Both quinpirole and dopamine significantly enhanced the rate of DOPA accumulation in the adrenals, indicating stimulation of adrenal tyrosine hydroxylase. The effect of dopamine was blocked by domperidone, a dopamine D2 receptor antagonist that penetrates poorly into the central nervous system. Thus the effect of dopamine, which itself penetrates poorly into the central nervous system, was presumably mediated peripherally. Similarly epinine, i.e. the N-methyl derivative of dopamine, appeared to enhance adrenal catecholamine synthesis, as indicated by an elevated adrenal dopamine level. The data support the view that stimulation of peripherally located dopamine D2-like receptors can enhance the rate of adrenal catecholamine synthesis by stimulating the activity of tyrosine hydroxylase.
我们先前以肾上腺多巴胺为指标，已获得证据表明喹吡罗和其他几种多巴胺D2样受体激动剂可急性刺激肾上腺儿茶酚胺的合成。在本研究中，我们采用在给予芳香族L-氨基酸脱羧酶抑制剂NSD 1015（3-羟基苄肼）后测定3,4-二羟基苯丙氨酸（DOPA）积累的方法，来测量喹吡罗和多巴胺对肾上腺中酪氨酸羟化作用的影响。鉴于肾上腺组织样本中儿茶酚胺含量很高，这就需要对分析DOPA的方法进行改进。喹吡罗和多巴胺均显著提高了肾上腺中DOPA的积累速率，表明肾上腺酪氨酸羟化酶受到了刺激。多巴胺的作用被多潘立酮阻断，多潘立酮是一种多巴胺D2受体拮抗剂，很难穿透进入中枢神经系统。因此，本身很难穿透进入中枢神经系统的多巴胺的作用，可能是通过外周介导的。同样，去甲肾上腺素，即多巴胺的N-甲基衍生物，似乎也能增强肾上腺儿茶酚胺的合成，肾上腺多巴胺水平升高表明了这一点。这些数据支持这样一种观点，即刺激外周的多巴胺D2样受体可通过刺激酪氨酸羟化酶的活性来提高肾上腺儿茶酚胺的合成速率。
