Barkey R J, Amit T, Ben-Shachar D, Youdim M B
Eur J Pharmacol. 1986 Mar 18;122(2):259-67. doi: 10.1016/0014-2999(86)90111-1.
Nutritional iron deficiency (ID), like neuroleptic treatment, results in a reduction in dopaminergic activity and a rise in serum prolactin (PRL). Since PRL has been shown to regulate its own receptors, we studied PRL binding sites during the above treatments. ID induced in 21 day old male rats for 28 days, or treatment with either chlorpromazine (10 mg/kg per day i.p.) or fluphenazine (5 mg/kg per day i.p.) for 21 days or haloperidol (5 mg/kg per day i.p.) for 9 days, caused significant increases (3- to 8-fold) in [125I]oPRL specific binding to the liver membranes. The combined treatment with haloperidol and ID, as above, resulted in an additive effect on hepatic PRL receptors, suggesting that the actions of neuroleptics and ID may be either submaximal or mediated by two different mechanisms. After 7 days or recovery from ID, the induced PRL receptors were completely reduced to the control values. In vitro desaturation of the induced PRL binding sites with MgCl2 caused a further increase (1.57-fold) in PRL binding. Characterization of the hepatic PRL binding sites induced by ID showed properties similar to those reported for the classical PRL receptors, including specificity for the lactogenic hormones, a high affinity constant (2.38 X 10(10) M-1) and inhibition of PRL binding to the induced receptors by an anti-PRL receptor antibody. The results of this study further support the suggested role of endogenous PRL in inducing its own receptors.
营养性缺铁(ID)与抗精神病药物治疗一样,会导致多巴胺能活性降低和血清催乳素(PRL)升高。由于已证明PRL可调节其自身受体,因此我们在上述治疗过程中研究了PRL结合位点。对21日龄雄性大鼠诱导缺铁28天,或用氯丙嗪(每天10mg/kg腹腔注射)或氟奋乃静(每天5mg/kg腹腔注射)治疗21天,或用氟哌啶醇(每天5mg/kg腹腔注射)治疗9天,均可使肝细胞膜上[125I]oPRL特异性结合显著增加(3至8倍)。如上述,氟哌啶醇与ID联合治疗对肝脏PRL受体产生相加作用,提示抗精神病药物和ID的作用可能是次最大效应,或由两种不同机制介导。缺铁7天后或恢复后,诱导产生的PRL受体完全降至对照值。用MgCl2对诱导的PRL结合位点进行体外去饱和处理,可使PRL结合进一步增加(1.57倍)。对ID诱导的肝脏PRL结合位点的特性分析表明,其特性与经典PRL受体报道的特性相似,包括对催乳激素的特异性、高亲和力常数(2.38×10(10)M-1)以及抗PRL受体抗体对PRL与诱导受体结合的抑制作用。本研究结果进一步支持内源性PRL在诱导其自身受体方面的作用。