The effects of L-dopa on in vitro and in vivo calcitonin release from medullary thyroid carcinoma.
The effects of L-dopa on in vitro and in vivo calcitonin release from medullary thyroid carcinoma.
复制标题
左旋多巴对甲状腺髓样癌体外和体内降钙素释放的影响。
DOI：
10.1210/jcem-48-3-408
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发表时间：
1979
期刊：
影响因子：
--
通讯作者：
M. Beaven
中科院分区：
文献类型：
--
作者：
S. Baylin;T. Hsu;S. Stevens;C. Kallman;D. Trump;M. Beaven
多巴胺前体左旋多巴对甲状腺髓样癌的基础和刺激降钙素释放的体内和体外作用进行了研究。在对5名患者进行的6项研究中，包括7- 8小时的对照期和试验期，口服左旋多巴使基础降钙素分泌平均下降35%;峰值效应发生在给药后30分钟内，持续时间长达4小时。在8例甲状腺髓样癌患者中的7例（3例输注钙，5例输注五肽胃泌素）中，左旋多巴在不同程度上抑制了刺激降钙素释放和总降钙素分泌的峰值水平;直接测试的基础降钙素水平在左旋多巴后也普遍平均下降了50%。在甲状腺髓样癌组织的短期器官培养系统中，降钙素分泌到培养基中与时间呈线性关系，持续2小时，并可被二丁酰cAMP和五肽胃泌素刺激。浓度为0.5- 3.0 mM的L-多巴抑制基础降钙素分泌（范围为25- 55%）。添加L-多巴脱羧酶抑制剂α-甲基多巴，消除了L-多巴的抑制作用。另一种L-多巴脱羧酶抑制剂卡比多巴在体外刺激降钙素分泌;这种作用可能不依赖于这种药物的L-多巴脱羧酶抑制特性，因为单独的α-甲基多巴不刺激降钙素分泌。它的结论是，胺前体L-多巴抑制降钙素释放甲状腺髓样癌患者的体外研究表明，这种影响的一部分可能涉及直接代谢的L-多巴多巴胺在肿瘤组织本身。考虑摄取的胺前体和随后的代谢这些化合物作为一个调节位点肽激素从外周内分泌组织释放的重要性强调。
The in vivo and in vitro effects of the dopamine precursor L-dopa on basal and stimulated calcitonin release from medullary thyroid carcinoma have been studied. In six studies of five patients, including 7- to 8-h control and test periods, oral L-dopa depressed basal calcitonin secretion by an average of 35%; the peak effects occurred within 30 min of drug administration and lasted for as long as 4 h. In seven of eight patients with medullary thyroid carcinoma (three infused with calcium and five with pentagastrin), L-dopa inhibited to varying degrees peak levels of stimulated calcitonin release and total calcitonin secretion; basal calcitonin levels, where directly tested, also again generally fell after L-dopa by an average of 50%. In a short term organ culture system using medullary thyroid carcinoma tissues, calcitonin secretion into the medium was linear with time for 2 h and could be stimulated by dibutyryl cAMP and pentagastrin. L-Dopa, in concentrations from 0.5--3.0 mM, inhibited basal calcitonin secretion (ranging from 25--55%). Addition of the L-dopa decarboxylase inhibitor, alpha-methyldopa, abolished the inhibitory effects of L-dopa. Another L-dopa decarboxylase inhibitor, carbidopa, stimulated calcitonin secretion in vitro; this effect may be independent of the L-dopa decarboxylase-inhibiting properties of this drug since alpha-methyldopa alone did not stimulate calcitonin secretion. It is concluded that the amine precursor L-dopa inhibits calcitonin release in patients with medullary thyroid carcinoma; the in vitro studies suggest that a portion of this effect may involve direct metabolism of L-dopa to dopamine in the tumor tissue itself. The importance of considering the uptake of amine precursors and the subsequent metabolism of these compounds as a modulating site for peptide hormone release from peripheral endocrine tissues is stressed.