Gasc J M, Shanmugam S, Sibony M, Corvol P
INSERM U36, Collège de France, Laboratoire de Médecine Expérimentale, Paris.
Hypertension. 1994 Nov;24(5):531-7. doi: 10.1161/01.hyp.24.5.531.
The angiotensin II type 1 (AT1) receptor in murine species exists as two isoforms (AT1A and AT1B) encoded by two different genes. Both subtypes have a 9/10 homology in the coding sequence of their mRNA. We examined organs of adult rats (liver, pituitary gland, adrenal gland, kidney, heart, and lung) to study the differential expression of these two genes in target tissues for angiotensin II. AT1A and AT1B mRNAs were detected by in situ hybridization using specific riboprobes for the 3' noncoding region of the mRNAs that have the lowest homology (approximately 6/10). Only AT1A was expressed in the liver, heart, and lung, and only AT1B was expressed in the anterior pituitary, where most cells were positive. In the adrenal gland, AT1A mRNA was detected in the zona glomerulosa and medulla and AT1B in the glomerulosa. In the kidney, AT1A mRNA was the predominant isoform (mesangial and juxtaglomerular cells, proximal tubules, vasa recta, and interstitial cells), but AT1B was also detected in mesangial and juxtaglomerular cells and in the renal pelvis. The results of this in situ detection suggest a tissue-selective regulation of AT1A and AT1B mRNAs. This tissue specificity may constitute a prerequisite condition if the two angiotensin II receptor subtypes, which are pharmacologically similar, are to selectively modulate the various effects of angiotensin II in the different target tissues.
在鼠类中,血管紧张素II 1型(AT1)受体以两种由不同基因编码的亚型(AT1A和AT1B)形式存在。两种亚型在其mRNA编码序列中具有9/10的同源性。我们检测了成年大鼠的器官(肝脏、垂体、肾上腺、肾脏、心脏和肺),以研究这两种基因在血管紧张素II靶组织中的差异表达。使用针对mRNA 3'非编码区(同源性最低,约为6/10)的特异性核糖探针,通过原位杂交检测AT1A和AT1B mRNA。仅AT1A在肝脏、心脏和肺中表达,仅AT1B在前叶垂体中表达,其中大多数细胞呈阳性。在肾上腺中,在球状带和髓质中检测到AT1A mRNA,在球状带中检测到AT1B mRNA。在肾脏中,AT1A mRNA是主要亚型(系膜细胞和球旁细胞、近端小管、直小血管和间质细胞),但在系膜细胞和球旁细胞以及肾盂中也检测到AT1B。这种原位检测结果表明AT1A和AT1B mRNA存在组织选择性调控。如果药理作用相似的两种血管紧张素II受体亚型要在不同靶组织中选择性调节血管紧张素II的各种作用,那么这种组织特异性可能构成一个先决条件。