Pfeiffer D G, Pfeiffer A, Almeida O F, Herz A
Department of Neuropharmacology, Max-Planck-Institut für Psychiatrie, Martinsried, Federal Republic of Germany.
J Endocrinol. 1987 Sep;114(3):469-76. doi: 10.1677/joe.0.1140469.
The involvement of mu- and kappa-opiate receptors in the regulation of LH and prolactin secretion was investigated in long-term ovariectomized rats using selective opiate receptor agonists and antagonists. The mu-agonists morphine and [D-Ala2,MePhe4,Gly5-ol]-enkephalin (DAGO) suppressed LH levels in a dose-related manner. The benzomorphane (-)-5,9-dimethyl-2'-hydroxy-2-(tetrahydrofurfuryl)-6,7-benzomorphan tartrate (MR 2034; a designated kappa-agonist) also suppressed LH levels, whereas another benzomorphane kappa-agonist (-)-5,9-dimethyl-2'-hydroxy-2-(2-methoxy-propyl)-6,7-benzomorphan hydrobromide (MRZ 2549) had no effect on the levels of this hormone. Pretreatment with the highly selective mu-antagonist beta-funaltrexamine (beta-FNA), the fumarate methyl ester derivative of naltrexone, blocked the actions of both mu-agonists and MR 2034, indicating that opiate suppression of LH secretion is mediated by mu-receptors. This was further confirmed by in-vitro studies: the KCl-induced release of LHRH from perifused hypothalami obtained from ovariectomized rats was significantly reduced by DAGO but not by MRZ 2549. Prolactin secretion was stimulated in a dose-dependent manner by both mu- and kappa-agonists. The stimulation caused by morphine and DAGO was antagonized by beta-FNA, whereas that caused by the kappa-agonists MR 2034 and MZR 2549 was resistant to blockade by beta-FNA but not by naloxone (an antagonist which blocks all classes of opiate receptors when given in high doses). Thus prolactin secretion seems to be regulated by both mu- and kappa-opiate receptors, whereas the effects on LH secretion seem to involve mu-receptors only.
利用选择性阿片受体激动剂和拮抗剂，在长期卵巢切除的大鼠中研究了μ和κ阿片受体在促黄体激素（LH）和催乳素分泌调节中的作用。μ激动剂吗啡和[D-丙氨酸2，甲硫氨酸4，甘氨酸5-醇]-脑啡肽（DAGO）以剂量相关的方式抑制LH水平。苯并吗啡烷（-）-5,9-二甲基-2'-羟基-2-（四氢糠基）-6,7-苯并吗啡烷酒石酸盐（MR 2034；一种指定的κ激动剂）也抑制LH水平，而另一种苯并吗啡烷κ激动剂（-）-5,9-二甲基-2'-羟基-2-（2-甲氧基丙基）-6,7-苯并吗啡烷氢溴酸盐（MRZ 2549）对该激素水平没有影响。用高选择性μ拮抗剂β-氟纳曲胺（β-FNA，纳曲酮的富马酸甲酯衍生物）预处理可阻断μ激动剂和MR 2034的作用，表明阿片类物质对LH分泌的抑制作用是由μ受体介导的。体外研究进一步证实了这一点：DAGO可显著降低去卵巢大鼠灌流下丘脑释放的氯化钾诱导的促性腺激素释放激素（LHRH），但MRZ 2549则无此作用。μ和κ激动剂均以剂量依赖的方式刺激催乳素分泌。吗啡和DAGO引起的刺激可被β-FNA拮抗，而κ激动剂MR 2034和MZR 2549引起的刺激对β-FNA的阻断有抗性，但对纳洛酮（一种高剂量时可阻断所有类型阿片受体的拮抗剂）的阻断敏感。因此，催乳素分泌似乎由μ和κ阿片受体共同调节，而对LH分泌的影响似乎仅涉及μ受体。
