LOCALIZATION OF ANGIOTENSIN-II TYPE-1 RECEPTOR SUBTYPE MESSENGER-RNA IN RAT-KIDNEY

The physiological effects of angiotensin II (ANG II) on the kidney are mediated primarily by the ANG II type 1 (AT(1)) receptor. Two highly similar AT(1) receptor subtypes have been identified in the rat by molecular cloning techniques, namely AT(1A) and AT(1B). The intrarenal localization of the AT(1A) and AT(1B) receptor subtypes has not been studied by hybridization methods with subtype-specific receptor probes. Using radiolabeled probes from the 3' noncoding region of the AT(1A) and AT(1B) cDNAs, we localized AT(1) mRNA in rat kidney by in situ hybridization. Specificity of the 3' noncoding region probes was tested by Northern blot and solution hybridization methods. AT(1A) mRNA levels were highest in the liver, kidney, and adrenal. In contrast, AT(1B) mRNA levels were highest in the adrenal and pituitary and low in kidney. Autoradiographic localization of I-125-[Sar(1),Ile(8)]ANG II binding indicated that the highest levels of AT(1) receptors were found in glomeruli and vascular elements. In situ hybridization with a nonselective AT(1) receptor riboprobe indicated that the highest levels of AT(1) 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 AT(1) subtype selective probes revealed that AT(1A) receptor mRNA was primarily localized to the vasa recta and diffusely to the outer stripe of the outer medulla and the renal cortex. The highest levels of AT(1B) mRNA were localized to the tip of the papilla corresponding to the ureter with low levels found within the vasa recta. These results indicate that the AT(1A) receptor subtype is the major form of AT(1) receptor expressed in rat kidney but leaves open the possibility that additional AT(1) receptors may be expressed in glomeruli.