Berry-Kravis E, Sklena P
Department of Pediatrics, University of Chicago, IL 60637.
Am J Med Genet. 1993 Jan 1;45(1):81-7. doi: 10.1002/ajmg.1320450120.
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.
对31名脆性X综合征患者、16名智力迟钝患者、4名自闭症患者和57名对照个体的血小板中的环磷酸腺苷（cAMP）生成情况进行了研究。使用1-异丁基-3-甲基黄嘌呤（IBMX）抑制磷酸二酯酶；使用前列腺素E1（PGE1）通过受体依赖性机制刺激cAMP生成，并使用福斯可林（FSK）直接激活催化亚基。相对于对照，脆性X血小板中，在IBMX、PGE1 + IBMX和FSK + IBMX中cAMP的生成分别为50%（P < 0.05）、65%（P = 0.001）和53%（P = 0.001）。智力迟钝或自闭症患者的cAMP生成与对照无统计学差异。年龄或性别对cAMP生成无影响。剂量反应曲线表明，cAMP生成异常是由于最大反应减弱而非刺激剂效力改变所致。此处呈现的数据表明，脆性X综合征患者的血小板中存在cAMP生成减少的情况。因此，脆性X大脑中cAMP介导的调节信号通路功能缺陷可能导致这些患者出现智力缺陷。
