Chang J P, Yu K L, Wong A O, Peter R E
Department of Zoology, University of Alberta, Edmonton, Canada.
Neuroendocrinology. 1990 Jun;51(6):664-74. doi: 10.1159/000125408.
Incubation of cultured goldfish pituitary cells with 10 nM to 1 microM apomorphine (APO), a non-selective dopamine agonist, increased growth hormone (GH) release in a dose-dependent manner. GH release was also stimulated in a dose-dependent manner by 0.1 nM to 1 microM salmon gonadotropin (GTH)-releasing hormone (sGnRH), sGnRH analog, and chicken GnRH-II (cGnRH-II). The magnitude of GH responses to 1 microM GnRHs were less than that to 1 microM APO. GH responses to 10 nM to 1 microM APO were not significantly increased by the addition of GnRHs. Static incubations with 0.1 nM to 1 microM of the dopamine D1 agonist SKF38393 did not alter basal GTH release, or the GTH responses to 10 nM sGnRH and cGnRH-II. In contrast, the D1 agonist SKF38393 significantly increased basal GH secretion with maximal stimulation achieved at 100 nM concentration, and GH responses to 10 nM sGnRH and 10 nM cGnRH-II were enhanced by simultaneous applications of SKF38393. Incubation with 1 microM of the D2 agonist LY171555 decreased basal GTH release. Additions of 0.1 nM to 1 microM LY171555 caused dose-dependent decreases in the GTH secretion induced by 10 nM sGnRH and cGnRH-II. In contrast, basal and GnRH-stimulated GH release were not affected by coincubations with LY171555. The D1 antagonist SKF83566 and the D2 antagonist domperidone, at 1 microM concentrations, specifically blocked the D1 agonist SKF38393-stimulated increase in GH release and the D2 agonist LY171555-induced depression of GTH secretion, respectively. In cell column perifusion studies, the D1 agonist SKF38393 at 0.1 nM to 1 microM had no effects on GTH release, but significantly elevated GH secretion rates when applied at 0.1-1 microM concentrations. The GH release induced by 1 microM SKF38393 was significantly reduced by simultaneous perifusion with 1 microM of the D1 antagonist SKF83566. Treatments with SKF38393 and/or SKF83566 did not affect net GTH and GH responses to sGnRH challenges. In contrast, perifusion with 0.1 and 1 microM of the D2 agonist LY171555 depressed basal as well as sGnRH-induced GTH responses. These effects of 1 microM LY171555 were completely blocked by simultaneous applications of 1 microM domperidone, a D2 antagonist. Treatments with these D2 selective drugs did not affect basal and sGnRH-stimulated GH release. These results indicate that in cultured goldfish pituitary cells, activation of dopamine D1- and D2-like receptors specifically stimulates GH release and inhibits both basal and stimulated GTH secretion, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)
用10 nM至1 microM阿扑吗啡（APO，一种非选择性多巴胺激动剂）培养金鱼垂体细胞，生长激素（GH）释放呈剂量依赖性增加。0.1 nM至1 microM鲑鱼促性腺激素（GTH）释放激素（sGnRH）、sGnRH类似物和鸡GnRH-II（cGnRH-II）也以剂量依赖性方式刺激GH释放。GH对1 microM GnRHs的反应幅度小于对1 microM APO的反应幅度。添加GnRHs后，GH对10 nM至1 microM APO的反应未显著增加。用0.1 nM至1 microM多巴胺D1激动剂SKF38393进行静态孵育，未改变基础GTH释放，也未改变GTH对10 nM sGnRH和cGnRH-II的反应。相反，D1激动剂SKF38393显著增加基础GH分泌，在100 nM浓度时达到最大刺激，同时应用SKF38393可增强GH对10 nM sGnRH和10 nM cGnRH-II的反应。用1 microM D2激动剂LY171555孵育可降低基础GTH释放。添加0.1 nM至1 microM LY171555导致10 nM sGnRH和cGnRH-II诱导的GTH分泌呈剂量依赖性降低。相反，基础和GnRH刺激的GH释放不受与LY171555共同孵育的影响。1 microM浓度的D1拮抗剂SKF83566和D2拮抗剂多潘立酮分别特异性阻断D1激动剂SKF38393刺激的GH释放增加和D2激动剂LY171555诱导的GTH分泌抑制。在细胞柱灌流研究中，0.1 nM至1 microM的D1激动剂SKF38393对GTH释放无影响，但在0.1 - 1 microM浓度应用时显著提高GH分泌率。同时用1 microM D1拮抗剂SKF83566灌流可显著降低1 microM SKF38393诱导的GH释放。用SKF38393和/或SKF83566处理不影响GTH和GH对sGnRH刺激的净反应。相反，用0.1和1 microM D2激动剂LY171555灌流可抑制基础以及sGnRH诱导的GTH反应。1 microM LY171555的这些作用被同时应用1 microM D2拮抗剂多潘立酮完全阻断。用这些D2选择性药物处理不影响基础和sGnRH刺激的GH释放。这些结果表明，在培养的金鱼垂体细胞中，多巴胺D1样和D2样受体的激活分别特异性刺激GH释放并抑制基础和刺激的GTH分泌。（摘要截断于400字）
