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大鼠心脏鸟氨酸脱羧酶的个体发生及其β-肾上腺素能反应性

Ontogeny of cardiac ornithine decarboxylase and its beta adrenergic responsiveness in the rat.

作者信息

Miska S P, Kimmel G L, Harmon J R, Webb P

出版信息

J Pharmacol Exp Ther. 1984 Aug;230(2):419-23.

PMID:6086887
Abstract

Ornithine decarboxylase (ODC) is a marker of tissue growth and development and, because sympathetic stimulation of beta adrenergic receptors acutely increases ODC in the adult rat heart, measurement of this enzyme can be used to indicate the functional intactness of the beta adrenergic receptor system in the heart. Changes in the postnatal ontogenetic pattern of this enzymatic activity may also indicate abnormal development and ODC appears to be particularly useful in evaluating the effects of prenatal insult on cardiac development. The present study examines the pattern of basal ODC activity and its developing sensitivity to beta adrenergic stimulation during the perinatal period in order to establish a data base for studies on the effect of various environmental agents on the developing cardiovascular system. ODC activity was measured in rat hearts on gestation day (GD) 20 through postnatal day (PND) 28 under saturating conditions of L-ornithine and pyridoxal 5-phosphate. Basal ODC activity fell from 3 nmol of CO2/hr/mg of protein at GD 20 to less than 0.5 nmol of CO2/hr/mg of protein at PND 18, rising again to nearly 1 nmol of CO2/hr/mg of protein at PND 22. The beta adrenergic agonist isoproterenol (10 mg/kg s.c.) resulted in peak ODC stimulation at 4 hr postinjection on PNDs 6, 14 and 21; however, no response was seen at PND 1 at this dose or at GD 20 (300 micrograms/kg s.c.). In dose-response studies, isoproterenol produced a maximal response at 10 mg/kg s.c., resulting in increases from control of 67, 230 and 1700% at PNDs 6, 14 and 21, respectively, indicating that the sensitivity of the heart to beta adrenergic stimulation increases with age, during the perinatal period.

摘要

鸟氨酸脱羧酶(ODC)是组织生长和发育的标志物,由于成年大鼠心脏中β肾上腺素能受体的交感神经刺激会使ODC急剧增加,因此对这种酶的测量可用于指示心脏中β肾上腺素能受体系统的功能完整性。这种酶活性的出生后个体发育模式的变化也可能表明发育异常,并且ODC在评估产前损伤对心脏发育的影响方面似乎特别有用。本研究检查围产期基础ODC活性的模式及其对β肾上腺素能刺激的发育敏感性,以便为研究各种环境因素对发育中的心血管系统的影响建立数据库。在L-鸟氨酸和磷酸吡哆醛饱和条件下,测量妊娠第20天(GD 20)至出生后第28天(PND 28)大鼠心脏中的ODC活性。基础ODC活性从GD 20时的3 nmol CO2/小时/毫克蛋白质降至PND 18时的低于0.5 nmol CO2/小时/毫克蛋白质,在PND 22时再次升至近1 nmol CO2/小时/毫克蛋白质。β肾上腺素能激动剂异丙肾上腺素(10 mg/kg皮下注射)在PND 6、14和21注射后4小时导致ODC刺激峰值;然而,在此剂量下PND 1或GD 20(300μg/kg皮下注射)未观察到反应。在剂量反应研究中,异丙肾上腺素在10 mg/kg皮下注射时产生最大反应,分别导致PND 6、14和21时比对照增加67%、230%和1700%,表明围产期心脏对β肾上腺素能刺激的敏感性随年龄增加。

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