Bagdy G, Calogero A E, Szemeredi K, Gomez M T, Murphy D L, Chrousos G P, Gold P W
Clinical Neuroendocrinology Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD 20892.
Brain Res. 1990 Dec 24;537(1-2):227-32. doi: 10.1016/0006-8993(90)90362-f.
Activation of serotonergic neurotransmission has been shown to increase plasma beta-endorphin-like immunoreactivity (beta-End-LI). To study the mechanism(s) of this action, we measured the effects of 3 potent serotonin (5-HT) agonists with different structures and 5-HT receptor binding profiles in conscious unrestrained Sprague-Dawley rats in vivo and in dispersed anterior pituicytes in vitro. The 5-HT1A agonist, 8-hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT), the 5-HT1C agonist, m-chlorophenylpiperazine (m-CPP), and the 5-HT2 agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), all markedly increased beta-End-LI in plasma in vivo. All 3 responses were blocked by dexamethasone pretreatment. Pituitary stalk transection (PST), as well as pretreatment with rabbit serum hyperimmune against rat corticotropin-releasing hormone (CRH, TS-6) completely abolished beta-End-LI response to 8-OH-DPAT and attenuated the responses by about 60% to DOI. Responses to m-CPP were markedly attenuated in PST rats, but pretreatment with TS-6 had no significant effect. To examine whether vasopressin (AVP) might be involved in the CRH neutralizing antibody-resistant beta-End-LI responses after m-CPP and DOI, we measured AVP concentrations after each agonist, m-CPP, but not DOI or 8-OH-DPAT, significantly elevated circulating AVP levels. As a proof of direct pituitary effect, DOI markedly stimulated beta-End-LI release from the anterior pituitary cell culture preparation in vitro. It was approximately as potent as CRH in the picomolar range, m-CPP was much less effective than DOI, while 8-OH-DPAT did not stimulate beta-End-LI release in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
血清素能神经传递的激活已被证明可增加血浆β-内啡肽样免疫反应性（β-End-LI）。为了研究这种作用的机制，我们在清醒不受限制的Sprague-Dawley大鼠体内以及体外分散的垂体前叶细胞中，测量了3种具有不同结构和5-羟色胺（5-HT）受体结合谱的强效5-羟色胺（5-HT）激动剂的作用。5-HT1A激动剂8-羟基-2-（二正丙基氨基）四氢萘（8-OH-DPAT）、5-HT1C激动剂间氯苯哌嗪（m-CPP）和5-HT2激动剂1-（2,5-二甲氧基-4-碘苯基）-2-氨基丙烷（DOI），在体内均显著增加血浆中的β-End-LI。所有这3种反应均被地塞米松预处理所阻断。垂体柄横断（PST）以及用抗大鼠促肾上腺皮质激素释放激素（CRH，TS-6）的兔血清超免疫预处理，完全消除了对8-OH-DPAT的β-End-LI反应，并使对DOI的反应减弱约60%。PST大鼠对m-CPP的反应明显减弱，但TS-6预处理无显著影响。为了研究加压素（AVP）是否可能参与m-CPP和DOI后对CRH中和抗体有抗性的β-End-LI反应，我们测量了每种激动剂作用后的AVP浓度，m-CPP而非DOI或8-OH-DPAT显著提高了循环中的AVP水平。作为垂体直接作用的证据，DOI在体外显著刺激垂体前叶细胞培养物释放β-End-LI。在皮摩尔范围内，它的效力与CRH大致相当，m-CPP的效力远低于DOI，而8-OH-DPAT在体外不刺激β-End-LI释放。（摘要截短于250字）
