Localization of angiotensin II type 1 receptor subtype mRNA in rat kidney.
The physiological effects of angiotensin II (ANG II) on the kidney are mediated primarily by the ANG II type 1 (AT1) receptor. Two highly similar AT1 receptor subtypes have been identified in the rat by molecular cloning techniques, namely AT1A and AT1B. The intrarenal localization of the AT1A and AT1B receptor subtypes has not been studied by hybridization methods with subtype-specific receptor probes. Using radiolabeled probes from the 3' noncoding region of the AT1A and AT1B cDNAs, we localized AT1 mRNA in rat kidney by in situ hybridization. Specificity of the 3' noncoding region probes was tested by Northern blot and solution hybridization methods. AT1A mRNA levels were highest in the liver, kidney, and adrenal. In contrast, AT1B mRNA levels were highest in the adrenal and pituitary and low in kidney. Autoradiographic localization of 125I-[Sar1,Ile8]ANG II binding indicated that the highest levels of AT1 receptors were found in glomeruli and vascular elements. In situ hybridization with a nonselective AT1 receptor riboprobe indicated that the highest levels of AT1 mRNA were in the outer medullary vasa recta and cortical glomeruli with additional diffuse labeling of the cortex and outer medulla, consistent with labeling of tubular elements. In contrast, in situ hybridization with the AT1 subtype selective probes revealed that AT1A receptor mRNA was primarily localized to the vasa recta and diffusely to the outer stripe of the outer medulla and the renal cortex.(ABSTRACT TRUNCATED AT 250 WORDS)
Healy
D P
DP
Department of Pharmacology, Mount Sinai School of Medicine, City University of New York, New York 10029.
Ye
M Q
MQ
Troyanovskaya
M
M
D015059:1-Sarcosine-8-Isoleucine Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001345:Autoradiography; D001483:Base Sequence; D001713:Biphenyl Compounds / Q000494:pharmacology; D015152:Blotting, Northern; D007093:Imidazoles / Q000494:pharmacology; D017403:In Situ Hybridization; D007668:Kidney / Q000378:metabolism*; D019808:Losartan; D008297:Male; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011945:Receptors, Angiotensin / Q000145:classification / Q000235:genetics*; D013777:Tetrazoles / Q000494:pharmacology; D014018:Tissue Distribution
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D012333:RNA, Messenger; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D015059:1-Sarcosine-8-Isoleucine Angiotensin II; D019808:Losartan