Chiarenza A, Lempereur L, Cantarella G, Barbera N, Maugeri M, Scapagnini U, Bernardini R
Institute of Pharmacology, University of Catania School of Medicine, Italy.
Pharmacol Toxicol. 1995 Jan;76(1):63-7. doi: 10.1111/j.1600-0773.1995.tb00104.x.
We have investigated the effects of the novel phospholipid drug glyceryl-phosphoryl-O-serine (GPS) on pituitary ACTH and hypothalamic corticotropin releasing hormone secretion in vitro in cultures from both 2- and 24 month-old Sprague-Dawley rats. Basal levels of ACTH in primary cultures of pituitary cells from 24 month-old rats were lower than (100 +/- 12 pg/10(5) cells) in 2 month-old rats (207 +/- 18 pg/10(5) cells). Basal medium corticotropin releasing hormone levels in hypothalamic cultures were higher in 24 month-old rats (45 +/- 7 pg/well/20 min.), than in 2 month-old rats (29 +/- 5.5 pg/well/20 min). Treatment of both pituitary cells with corticotropin releasing hormone and hypothalami with serotonin resulted respectively in a significant, concentration-dependent, increase of medium ACTH and corticotropin releasing hormone. However, concentration-response curves for ACTH and corticotropin releasing hormone were shifted to the right in cultures from 24 month-old rats. Incubation with graded concentrations of GPS produced significant increase in medium ACTH and corticotropin releasing hormone in cultures from 24 month-old rats, whereas the drug was ineffective in stimulating secretion of both hormones from 2 month-old rat cells. In addition, the adenylate cyclase stimulator forskolin and the protein kinase C activator oleyl-acyl-glycerol stimulated ACTH secretion in pituicytes from rats of both ages. However, response to oleyl-acyl-glycerol was blunted in pituicytes from 24 month-old rats. Combination of either forskolin or oleyl-acyl-glycerol with GPS resulted in a potentiation of the effect. Our data confirm an impairment of both pituitary ACTH and hypothalamic corticotropin releasing hormone secretion in the aging rat.(ABSTRACT TRUNCATED AT 250 WORDS)
我们研究了新型磷脂药物甘油磷酰 - O - 丝氨酸（GPS）对2月龄和24月龄Sprague - Dawley大鼠体外培养的垂体促肾上腺皮质激素（ACTH）和下丘脑促肾上腺皮质激素释放激素分泌的影响。24月龄大鼠垂体细胞原代培养中ACTH的基础水平低于2月龄大鼠（207±18 pg/10⁵细胞，24月龄大鼠为100±12 pg/10⁵细胞）。下丘脑培养物中基础培养基促肾上腺皮质激素释放激素水平在24月龄大鼠中更高（45±7 pg/孔/20分钟），高于2月龄大鼠（29±5.5 pg/孔/20分钟）。用促肾上腺皮质激素释放激素处理垂体细胞以及用血清素处理下丘脑分别导致培养基中ACTH和促肾上腺皮质激素释放激素显著的、浓度依赖性增加。然而，24月龄大鼠培养物中ACTH和促肾上腺皮质激素释放激素的浓度 - 反应曲线向右移动。用不同浓度的GPS孵育24月龄大鼠培养物可使培养基中ACTH和促肾上腺皮质激素释放激素显著增加，而该药物对刺激2月龄大鼠细胞分泌这两种激素无效。此外，腺苷酸环化酶刺激剂福斯高林和蛋白激酶C激活剂油酰 - 酰基甘油刺激了两个年龄段大鼠垂体细胞中ACTH的分泌。然而，24月龄大鼠垂体细胞对油酰 - 酰基甘油的反应减弱。福斯高林或油酰 - 酰基甘油与GPS联合使用可增强效果。我们的数据证实了衰老大鼠垂体ACTH和下丘脑促肾上腺皮质激素释放激素分泌均受损。（摘要截短至250字）
