DEMONSTRATION OF ABNORMAL CYCLIC-AMP PRODUCTION IN PLATELETS FROM PATIENTS WITH FRAGILE-X SYNDROME
DEMONSTRATION OF ABNORMAL CYCLIC-AMP PRODUCTION IN PLATELETS FROM PATIENTS WITH FRAGILE-X SYNDROME
复制标题
DOI：
10.1002/ajmg.1320450120
复制
发表时间：
1993-01-01
期刊：
影响因子：
--
通讯作者：
SKLENA, P
中科院分区：
文献类型：
--
作者：
BERRYKRAVIS, E;SKLENA, P
研究了31例脆性X综合征患者、16例精神发育迟滞患者、4例自闭症患者和57例对照者血小板中环磷酸腺苷的产生。1-异丁基-3-甲基黄嘌呤（IBMX）用于抑制磷酸二酯酶;前列腺素E1（PGE 1）用于通过受体依赖性机制刺激cAMP产生，毛喉素（FSK）用于直接激活催化亚基。在脆性X血小板中，IBMX、PGE 1 + IBMX和FSK + IBMX的环AMP产量分别为对照组的50%（P < 0.05）、65%（P = 0.001）和53%（P = 0.001）。在精神发育迟滞或自闭症患者中，环磷酸腺苷的产生与对照组无统计学差异。年龄或性别对cAMP的产生没有影响。剂量反应曲线表明，异常的cAMP生产是由于减少最大反应，而不是改变刺激剂的效力。本文提供的数据表明，脆性X综合征患者的血小板中存在减少的cAMP产生。因此，cAMP介导的调节信号通路在脆性X脑功能缺陷可能有助于在这些患者的精神缺陷。
Cyclic AMP production was studied in platelets from 31 patients with fragile X syndrome, 16 patients with mental retardation, 4 patients with autistic disorder, and 57 control individuals. 1-isobutyl-3-methylxanthine (IBMX) was used to inhibit phosphodiesterase; prostaglandin E1 (PGE1), to stimulate cAMP production via a receptor-dependent mechanism, and forskolin (FSK), to directly activate the catalytic subunit. Cyclic AMP production in IBMX, PGE1 + IBMX, and FSK + IBMX was 50% (P < 0.05), 65% (P = 0.001), and 53% (P = 0.001), respectively, in fragile X platelets relative to controls. Cyclic AMP production was not statistically different from controls in patients with mental retardation or autistic disorder. There was no effect of age or sex on cAMP production. Dose response curves suggested that abnormal cAMP production was due to diminished maximal response rather than altered potency of stimulating agents. The data presented here demonstrate that diminished cAMP production exists in platelets from patients with fragile X Syndrome. Thus, defective functioning of cAMP-mediated regulatory signalling pathways in fragile X brain may contribute to the mental deficiency in these patients.