DIFFERENTIAL REGULATION OF NATRIURETIC PEPTIDE RECEPTOR MESSENGER-RNAS DURING THE DEVELOPMENT OF CARDIAC-HYPERTROPHY IN THE RAT
DIFFERENTIAL REGULATION OF NATRIURETIC PEPTIDE RECEPTOR MESSENGER-RNAS DURING THE DEVELOPMENT OF CARDIAC-HYPERTROPHY IN THE RAT
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DOI：
10.1172/jci116887
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发表时间：
1993-12-01
影响因子：
15.9
通讯作者：
WILKINS, MR
中科院分区：
文献类型：
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作者：
BROWN, LA;NUNEZ, DJR;WILKINS, MR
心脏表达三种利钠肽受体(NPR)，即NPR-A、NPR-B和NPR-C。本实验研究了心钠素(ANP)和脑利钠肽(BNP)基因转录产物在大鼠动静脉腔静脉瘘心肌肥大过程中的表达及其受体之间的时间关系。采用基因扩增的方法检测信使RNA。进行性心肌肥厚伴随着整个心脏ANP信使核糖核酸的增加和左心房BNP信使核糖核酸的增加。最引人注目的观察是NPR-C转录本(假定的‘’清除‘’受体)在所有的小室中逐渐消失；这与NPR-A和NPR-B(鸟苷酸环化酶连接的受体)的mRNA水平的增加形成鲜明对比。如果转录本的变化反映在受体蛋白水平，我们的观察具有重要的治疗意义，因为(A)NPR-C的明显下调可能会增强钠尿肽对心脏的局部作用，以及(B)NPR-C的丢失，特别是如果它广泛存在，可能会降低钠尿肽的消除速度，限制旨在减少肽清除的特定NPR-C配体的治疗潜力。
The heart expresses the three natriuretic peptide receptors (NPR), namely NPR-A, NPR-B, and NPR-C. We have examined the temporal relationship between the expression of mRNA transcripts for atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) and their receptors in the heart during the development of cardiac hypertrophy in the aortovenocaval fistula rat. Messenger RNAs were measured by cDNA amplification. Progressive cardiac hypertrophy was accompanied by increased ANP mRNA prevalence throughout the heart and increased BNP mRNA in the left atrium. The most striking observation was the gradual disappearance of NPR-C transcripts (the putative ''clearance'' receptor) in all chambers; this was in marked contrast to the increase in mRNA levels for NPR-A and NPR-B (the guanylyl cyclase-linked receptors). Our observations have important therapeutic implications if the transcript changes are mirrored at the receptor protein level because (a) the apparent down-regulation of NPR-C may enhance the local action of natriuretic peptides on the heart, and (b) the loss of NPR-C, particularly if it is widespread, may reduce the rate of elimination of the natriuretic peptides, restricting the therapeutic potential of specific NPR-C ligands designed to reduce peptide clearance.