Volpi R, Coiro V, Castelli A, Cappagli M, Muzzetto P, Sciarra A, Chiodera P
Horm Metab Res. 1984 Dec;16 Suppl 1:131-3. doi: 10.1055/s-2007-1014916.
Dopamine (DA) has a physiological role in the control of GH release from the pituitary. Studies have been carried out using DA agonist or antagonist, since in normal subjects DA does not cross the blood-brain-barrier (BBB). In contrast, the BBB is altered in type I diabetics, who respond to DA with a significant increase of GH release. In these patients Metoclopramide (MCP), an antidopaminergic drug, is also capable of stimulating GH release. In a previous paper, we suggested that this effect could be related to enhanced blood concentrations of DA, due to a reduced peripheral DA catabolism determined by MCP. However, since MCP crosses the BBB, an effect of this drug on other hypothalamic neurotransmitters could not be excluded. The purpose of the present study was to determine whether Domperidone (DOM) a drug which does not cross the BBB, but as well as MCP is thought to increase blood levels of DA, is also capable of inducing GH release in diabetics. Sixteen type I male diabetics were injected intravenously with MCP (6) or DOM (10) and a week later with normal saline. Ten normal subjects participated as controls to all three tests. MCP and DOM did not produce any effects in the normal controls; as expected, MCP induced a marked increase in serum levels of GH in the diabetics, while in contrast DOM did not stimulate GH secretion in diabetics. These data suggest that the effect of MCP is not due to the dopaminergic pathway previously described, but rather to a modulation of some other neurotransmitter at hypothalamic level, or to a direct effect on the pituitary in diabetics.
多巴胺（DA）在控制垂体生长激素（GH）释放方面具有生理作用。由于在正常受试者中多巴胺无法穿过血脑屏障（BBB），因此已使用多巴胺激动剂或拮抗剂进行了相关研究。相比之下，I型糖尿病患者的血脑屏障发生了改变，他们对多巴胺的反应是GH释放显著增加。在这些患者中，抗多巴胺能药物甲氧氯普胺（MCP）也能够刺激GH释放。在之前的一篇论文中，我们认为这种效应可能与多巴胺血浓度升高有关，这是由MCP导致的外周多巴胺分解代谢减少所致。然而，由于MCP能够穿过血脑屏障，因此不能排除该药物对其他下丘脑神经递质的影响。本研究的目的是确定多潘立酮（DOM），一种不能穿过血脑屏障但与MCP一样被认为会增加多巴胺血浓度的药物，是否也能够在糖尿病患者中诱导GH释放。16名I型男性糖尿病患者静脉注射MCP（6例）或DOM（10例），一周后注射生理盐水。10名正常受试者作为所有三项测试的对照。MCP和DOM在正常对照组中未产生任何影响；正如预期的那样，MCP在糖尿病患者中诱导血清GH水平显著升高，而相比之下，DOM并未刺激糖尿病患者的GH分泌。这些数据表明，MCP的作用并非归因于先前描述的多巴胺能途径，而是由于下丘脑水平上其他神经递质的调节，或者是对糖尿病患者垂体的直接作用。
