Slotkin T A, Kudlacz E M, Lappi S E, Tayyeb M I, Seidler F J
Department of Pharmacology Duke University Medical Center, Durham, North Carolina 27710.
Life Sci. 1990;47(22):2051-7. doi: 10.1016/0024-3205(90)90440-3.
beta-Adrenergic agonists used in therapy of premature labor and asthma cross the placenta and can affect development of the fetal nervous system. In the current study, pregnant rats were given 10 mg/kg of terbutaline on gestational days 17, 18 and 19 and adrenergic receptor binding capabilities examined in brain regions of the offspring. Despite the absence of body or brain growth impairment, selective increases were seen postnatally in cerebellar alpha 1- and alpha 2-receptor subtypes, whereas the same receptor populations were decreased by small amounts in cerebral cortex and midbrain + brainstem. beta-Adrenergic receptors showed little or no change in any region. The regional and subtype selectivity are compatible with primary deficits in the development of noradrenergic projections to the cerebellum identified in previous studies and provide further evidence that therapeutic use of beta-adrenergic agonists may produce neurobehavioral teratology.
用于早产和哮喘治疗的β-肾上腺素能激动剂可穿过胎盘,并可能影响胎儿神经系统的发育。在本研究中,在妊娠第17、18和19天给怀孕大鼠注射10mg/kg的特布他林,并检测其后代脑区的肾上腺素能受体结合能力。尽管未出现身体或脑生长受损的情况,但产后在小脑α1和α2受体亚型中出现了选择性增加,而在大脑皮层和中脑+脑干中,相同的受体群体则有少量减少。β-肾上腺素能受体在任何区域均显示出很少或没有变化。这种区域和亚型选择性与先前研究中确定的去甲肾上腺素能投射到小脑发育中的原发性缺陷相符,并进一步证明β-肾上腺素能激动剂的治疗应用可能会产生神经行为致畸作用。